leptin and Hypertension

Hypertension is inheritable, and some candidate genes such as leptin and adiponectin have drawn special concerns.. We performed a meta-analysis on the association of 7 genetic variants in genes encoding leptin, leptin receptor and adiponectin with hypertension risk and circulating leptin/adiponectin changes.. Literature search, report selection and data extraction were performed by two authors independently. Effect sizes are expressed as odds ratio (OR) or standard mean difference (SMD) with 95% confidence interval (CI).. Our findings indicated that leptin gene rs7799039 and (TTTC)

Topics: Adiponectin; Genotype; Humans; Hypertension; Leptin; Polymorphism, Single Nucleotide; Receptors, Leptin

Endothelial dysfunction is a major risk factor for many cardiovascular diseases, notably hypertension. Obesity increases the risk of endothelial dysfunction in association with increasing production of the adipokine leptin. Preclinical studies have begun to unravel the mechanisms whereby leptin leads to the development of endothelial dysfunction, which are sex-specific. This review will summarize recent findings of mechanisms of leptin-induced endothelial impairment in both male and females and in pregnancy.. Leptin receptors are found in high concentrations in the central nervous system (CNS), via which leptin promotes appetite suppression and upregulates sympathetic nervous system activation. However, leptin receptors are expressed in many other tissues, including the vascular endothelial cells and smooth muscle cells. Recent studies in mice with vascular endothelial or smooth muscle-specific knockdown demonstrate that endothelial leptin receptor activation plays a protective role against endothelial dysfunction in male animals, but not necessarily in females. Clinical studies indicate that women may be more sensitive to obesity-associated vascular endothelial dysfunction. Emerging preclinical data indicates that leptin and progesterone increase aldosterone production and endothelial mineralocorticoid receptor activation, respectively. Furthermore, decades of clinical studies indicate that leptin levels increase in the hypertensive pregnancy disorder preeclampsia, which is characterized by systemic endothelial dysfunction. Leptin infusion in mice induces the clinical characteristics of preeclampsia, including endothelial dysfunction.. Novel preclinical data indicate that the mechanisms whereby leptin promotes endothelial dysfunction are sex-specific. Leptin-induced endothelial dysfunction may also play a role in hypertensive pregnancy as well.

Topics: Animals; Endothelial Cells; Female; Humans; Hypertension; Leptin; Male; Mice; Obesity; Pre-Eclampsia; Receptors, Leptin

Obesity has recently emerged as one of the most severe health concerns. Obesity is a key autonomous risk factor for heart failure and contributes to cardiovascular disease (CVD) risk factors such as hypertension, type 2 diabetes, and metabolic abnormalities. Obesity is caused by a metabolic imbalance, which occurs when calories burnt are fewer than the number of calories consumed. There are several pathways accountable for the adverse impacts of obesity on the cardiovascular system. Inflammatory cell infiltration develops in the adipose tissue, the pancreas, and other issues similar to the progression of obesity. Inflammation is triggered by immune cells that invade dysfunctional adipose tissue. The atherosclerotic inflammation phase, related to obesity, induces coronary calcification. Obesity is linked to elevated levels of leptin and high blood pressure. Leptin causes systemic vasoconstriction, sodium retention, and increased blood pressure by influencing the synthesis of nitric oxide and activating the sympathetic nervous system. Obesity is a well-known risk factor for CVD and is one of the leading causes of the greater risk of diseases, including dyslipidemia, hypertension, depression, metabolic syndrome, atrial fibrillation, and heart failure in adults and children. When used with dietary improvements, antiobesity drugs improve the probability of experiencing clinically healthy (5%) weight loss. This review aimed to address the consequences of obesity on cardiac structure and function, risk factors, the impact of the obesity paradox, pharmacological treatment strategies for managing and recommended exercise and diet.

Topics: Adult; Cardiovascular Diseases; Child; Diabetes Mellitus, Type 2; Heart Failure; Humans; Hypertension; Inflammation; Leptin; Obesity

Cardiovascular and metabolic complications associated with excess adiposity are linked to chronic activation of the sympathetic nervous system, resulting in a high risk of mortality among obese individuals. Obesity-related positive energy balance underlies the progression of hypertension, end-organ damage, and insulin resistance, driven by increased sympathetic tone throughout the body. It is, therefore, important to understand the central network that drives and maintains sustained activation of the sympathetic nervous system in the obese state. Experimental and clinical studies have identified structural changes and altered dynamics in both grey and white matter regions in obesity. Aberrant activation in certain brain regions has been associated with altered reward circuitry and metabolic pathways including leptin and insulin signaling along with adiposity-driven systemic and central inflammation. The impact of these pathways on the brain via overactivity of the sympathetic nervous system has gained interest in the past decade. Primarily, the brainstem, hypothalamus, amygdala, hippocampus, and cortical structures including the insular, orbitofrontal, temporal, cingulate, and prefrontal cortices have been identified in this context. Although the central network involving these structures is much more intricate, this review highlights recent evidence identifying these regions in sympathetic overactivity in obesity.

Topics: Brain; Humans; Hypertension; Insulin Resistance; Leptin; Obesity; Sympathetic Nervous System

Respiratory viruses are associated with significant global morbidity and mortality, as well as socioeconomic factors. Certain conditions and patient groups are more susceptible to develop severe viral respiratory tract infections (RTIs).. To summarise the data on deregulated immune pathways that have been associated with increased susceptibility to severe viral RTIs in certain populations. We also describe the commonalities of the defective immune pathways across these susceptible populations that may represent possible targets for future therapeutic or preventative approaches.. We conducted free searches in Medline, Scopus, and Google Scholar for studies focusing on potential mechanisms of immune dysfunction that may be associated with severe viral RTIs in susceptible populations with conditions including pregnancy, obesity, diabetes mellitus, hypertension, cardiovascular disease, asthma, chronic obstructive pulmonary disease (COPD), chronic kidney disease, and extremes of age. We considered preclinical/animal data, original human studies, and reviews.. Innate and adaptive immune responses become quantitatively and qualitatively compromised in aging, obesity, and diabetes mellitus, with the most pronounced changes affecting T cells. Moreover, immune dysregulation by the so-called inflamm-aging results in chronic low-grade inflammation in such conditions. Increased leptin levels affect the immune system particularly in obesity, while leptin dysregulation plays a role in asthma and COPD pathogenesis. Deficient production of interferon (IFN) type I and III in response to rhinovirus contributes to asthma exacerbations. Similar attenuation of IFN production in response to influenza and rhinovirus has been documented in pregnancy. Dampened type I IFN responses have also been found in diet-induced obese mice and in obese individuals.. Immunosenescence and chronic low-grade inflammation accompanying aging and a variety of chronic conditions, such as diabetes, obesity, asthma, COPD, chronic renal disease, and hypertension, contribute to the poor outcomes observed following viral respiratory infections. Commonly affected pathways may represent potential future therapeutic targets.

Topics: Animals; Asthma; Disease Susceptibility; Enterovirus Infections; Humans; Hypertension; Immunity; Inflammation; Interferons; Leptin; Mice; Obesity; Pneumonia; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Infections; Rhinovirus

The World Health Organization (WHO) refers to obesity as abnormal or excessive fat accumulation that presents a health risk. Obesity was first designated as a disease in 2012 and since then the cost and the burden of the disease have witnessed a worrisome increase. Obesity and hypertension are closely interrelated as abdominal obesity interferes with the endocrine and immune systems and carries a greater risk for insulin resistance, diabetes, hypertension, and cardiovascular disease. Many factors are at the interplay between obesity and hypertension. They include hemodynamic alterations, oxidative stress, renal injury, hyperinsulinemia, and insulin resistance, sleep apnea syndrome and the leptin-melanocortin pathway. Genetics, epigenetics, and mitochondrial factors also play a major role. The measurement of blood pressure in obese patients requires an adapted cuff and the search for other secondary causes is necessary at higher thresholds than the general population. Lifestyle modifications such as diet and exercise are often not enough to control obesity, and so far, bariatric surgery constitutes the most reliable method to achieve weight loss. Nonetheless, the emergence of new agents such as Semaglutide and Tirzepatide offers promising alternatives. Finally, several molecular pathways are actively being explored, and they should significantly extend the treatment options available.

Topics: Humans; Hypertension; Insulin Resistance; Leptin; Melanocortins; Obesity

Lipodystrophy syndromes (LS) constitute a group of rare diseases of the adipose tissue, characterized by a complete or selective deficiency of the fat mass. These disorders are associated with important insulin resistance, cardiovascular and metabolic comorbidities that impact patient's survival and quality of life. Management is challenging and includes diet, physical activity, and specific pharmacological treatment of LS-associated comorbidities. Because of a common pathophysiology involving decreased concentration of the adipokine leptin, efforts have been made to develop therapeutic strategies with leptin replacement therapy. Metreleptin, a recombinant human leptin analogue, has been proposed in hypoleptinemic patients since the beginning of 2000's. The treatment leads to an improvement in metabolic parameters, more important in generalized than in partial LS forms. In this review, the current knowledge about the development of the drug, its outcomes in the treatment of lipodystrophic patients as well as the peculiarities of its use will be presented.

Topics: Autoimmune Diseases; Bone and Bones; Dyslipidemias; Fatty Liver; Glucose; Humans; Hyperglycemia; Hypertension; Kidney; Leptin; Lipid Metabolism; Lipodystrophy; Quality of Life; Recombinant Proteins; Reproduction; Syndrome

Far beyond the compelling proofs supporting that the metabolic syndrome represents a risk factor for diabetes and cardiovascular diseases, a growing body of evidence suggests that it is also a risk factor for different types of cancer. However, the involved molecular mechanisms underlying this association are not fully understood, and they have been mainly focused on the individual contributions of each component of the metabolic syndrome such as obesity, hyperglycemia, and high blood pressure to the development of cancer. The Receptor for Advanced Glycation End-products (RAGE) axis activation has emerged as an important contributor to the pathophysiology of many clinical entities, by fueling a chronic inflammatory milieu, and thus supporting an optimal microenvironment to promote tumor growth and progression. In the present review, we intend to highlight that RAGE axis activation is a crosswise element on the potential mechanistic contributions of some relevant components of metabolic syndrome into the association with cancer.

Topics: Adiponectin; Adipose Tissue; Animals; Disease Progression; Gene Expression Regulation; Humans; Hyperglycemia; Hypertension; Inflammation; Insulin-Like Growth Factor I; Leptin; Ligands; Metabolic Syndrome; Mice; Neoplasms; Obesity; Peroxisome Proliferator-Activated Receptors; Rats; Receptor for Advanced Glycation End Products; Signal Transduction; Vascular Endothelial Growth Factor A; Wnt Proteins

Obesity represents the single greatest ongoing roadblock to improving cardiovascular health. Prolonged obesity is associated with fundamental changes in the integrative control of energy balance, including the development of selective leptin resistance, which is thought to contribute to obesity-associated hypertension, and adaptation of resting metabolic rate (RMR) when excess weight is reduced. Leptin and the melanocortin system within the hypothalamus contribute to the control of both energy balance and blood pressure. While the development of drugs to stimulate RMR and thereby reverse obesity through activation of the melanocortin system has been pursued, most of the resulting compounds simultaneously cause hypertension. Evidence supports the concept that although feeding behaviors, RMR, and blood pressure are controlled through mechanisms that utilize similar molecular mediators, these mechanisms exist in anatomically dissociable networks. New evidence supports a major change in molecular signaling within AgRP (Agouti-related peptide) neurons of the arcuate nucleus of the hypothalamus during prolonged obesity and the existence of multiple distinct subtypes of AgRP neurons that individually contribute to control of feeding, RMR, or blood pressure. Finally, ongoing work by our laboratory and others support a unique role for AT

Topics: Angiotensins; Cardiometabolic Risk Factors; Central Nervous System; Drug Discovery; Humans; Hypertension; Leptin; Metabolism; Obesity

Hyperinsulinemia and insulin resistance were proposed more than 30 years ago to be important contributors to elevated blood pressure (BP) associated with obesity and the metabolic syndrome, also called syndrome X. Support for this concept initially came from clinical and population studies showing correlations among hyperinsulinemia, insulin resistance, and elevated BP in individuals with metabolic syndrome. Short-term studies in experimental animals and in humans provided additional evidence that hyperinsulinemia may evoke increases in sympathetic nervous system (SNS) activity and renal sodium retention that, if sustained, could increase BP. Although insulin infusions may increase SNS activity and modestly raise BP in rodents, chronic insulin administration does not significantly increase BP in lean or obese insulin-resistant rabbits, dogs, horses, or humans. Multiple studies in humans and experimental animals have also shown that severe insulin resistance and hyperinsulinemia may occur in the absence of elevated BP. These observations question whether insulin resistance and hyperinsulinemia are major factors linking obesity/metabolic syndrome with hypertension. Other mechanisms, such as physical compression of the kidneys, activation of the renin-angiotensin-aldosterone system, hyperleptinemia, stimulation of the brain melanocortin system, and SNS activation, appear to play a more critical role in initiating hypertension in obese subjects with metabolic syndrome. However, the metabolic effects of insulin resistance, including hyperglycemia and dyslipidemia, appear to interact synergistically with increased BP to cause vascular and kidney injury that can exacerbate the hypertension and associated injury to the kidneys and cardiovascular system.

Topics: Animals; Humans; Hyperinsulinism; Hypertension; Insulin Resistance; Kidney; Leptin; Metabolic Syndrome; Obesity; Renin-Angiotensin System; Sodium; Sympathetic Nervous System

The adipokine leptin is expressed at higher concentrations in obese subjects, who also incidentally have a higher prevalence of hypertension. The pathogenesis of this obesity-related hypertension is controversial and is believed to be related to many factors including increased sympathetic activity, abnormalities of the renin-angiotensin system, sodium retention, and an endotheliopathy acting independently or in concert with increased circulating leptin. This review discusses the potential mechanisms through which changes in leptin signal transduction pathways in tissues with the leptin receptor, especially the hypothalamus, mediate the pathogenetic relationships between obesity and hypertension. The hypothesis is explored that leptin effects on blood pressure (BP) are meditated by the downstream effects of hypothalamic leptin signaling and ultimately result in activation of specific melanocortin receptors located on sympathetic neurons in the spinal cord. The physiological consequences of this sympathetic activation of the heart and kidney are activation of the renin-angiotensin system, sodium retention and circulatory expansion and finally, elevated BP. This sequence of events has been elegantly demonstrated with leptin infusion and gene knockout studies in animal models but has not been convincingly reproducibly confirmed in humans. Further studies in human subjects on the specific roles of hypothalamic leptin in essential hypertension are indicated as elucidation of the signaling pathways should provide better understanding of the role of weight loss in BP control and afford an additional mechanism for pharmacologic control of BP in adults and children at risk of cardiovascular disease.

Topics: Animals; Gene Deletion; Genotype; Humans; Hypertension; Hypothalamus; Kidney; Leptin; Mice; Obesity; Pro-Opiomelanocortin; Promoter Regions, Genetic; Signal Transduction; Spinal Cord; Sympathetic Nervous System

To review the latest reports of the contributions of the endothelial mineralocorticoid receptor to endothelial dysfunction and hypertension to begin to determine the clinical potential for this pathway for hypertension treatment.. Endothelial mineralocorticoid receptor expression is sex-specifically increased in female mice and humans compared with males. Moreover, the expression of endothelial mineralocorticoid receptors is increased by endothelial progesterone receptor activation and naturally occurring fluctuations in progesterone levels (estrous, pregnancy) predict endothelial mineralocorticoid receptor expression levels in female mice. These data follow many previous reports that have indicated that endothelial mineralocorticoid receptor deletion is protective in the development of obesity- and diabetes-associated endothelial dysfunction in female mouse models. These studies have more recently been followed up by reports indicating that both intact endothelial mineralocorticoid receptor and progesterone receptor expression are required for obesity-associated, leptin-mediated endothelial dysfunction in female mice. In addition, the intra-endothelial signaling pathway for endothelial mineralocorticoid receptors to induce dysfunction requires the intact expression of α-epithelial sodium channels (αENaC) in endothelial cells in females. Endothelial mineralocorticoid receptors are sex-specifically upregulated in the vasculature of females, a sex difference which is driven by endothelial progesterone receptor activation, and increased activity of these endothelial mineralocorticoid receptors is a crucial mediator of endothelial dysfunction, and potentially hypertension, in obese female experimental models.

Topics: Aldosterone; Animals; Disease Models, Animal; Endothelial Cells; Endothelium, Vascular; Epithelial Sodium Channels; Female; Humans; Hypertension; Leptin; Male; Mice; Mineralocorticoid Receptor Antagonists; Obesity; Receptors, Mineralocorticoid; Receptors, Progesterone; Sex Factors; Vascular Diseases

Chronic sympathetic nervous system overactivity is a hallmark of aging and obesity and contributes to the development of cardiovascular diseases including hypertension and heart failure. The cause of this chronic sympathoexcitation in aging and obesity is multifactorial and centrally mediated. In this mini-review, we have provided an overview of the key and emerging central mechanisms contributing to the pathogenesis of sympathoexcitation in obesity and healthy aging, specifically focusing on hypertension. A clear understanding of these mechanisms will pave way for targeting the sympathetic nervous system for the treatment of cardiovascular diseases in obesity and aging.

Topics: Aging; Animals; Cardiovascular Diseases; Cellular Senescence; Humans; Hypertension; Inflammation; Leptin; Obesity; Oxidative Stress; Renin-Angiotensin System; Sympathetic Nervous System

The prominence of obesity in the clinical population as well as the strong association of cardiovascular risk factors with obesity has prompted the investigation of the adipose tissue and its physiological contribution to cardiovascular health. A notable finding in these investigations was the discovery of the adipocyte-derived hormone leptin. Leptin is secreted from the adipose tissue, increases in linear fashion in the circulation with increased body mass and is implicated in the development of cardiovascular disease in obesity, notably via pro-hypertensive mechanisms. Leptin stimulates the activation of the sympathetic nervous system in male patients and mice, which has been implicated as the pro-hypertensive pathway for leptin in obesity. However, obese premenopausal females do not exhibit increased sympathetic activation in response to hyperleptinemia in obesity, indicating a sex-discrepancy in mechanisms of obesity-associated hypertension. Our lab recently demonstrated that leptin also induces the adrenal production of aldosterone in a direct fashion and that this pathway leads to the hyperaldosteronemia that is characteristic of obesity. We have also published data that indicate that the implications of leptin-induced aldosterone are of particular impact in obese females. Leptin-mediated hypertension and endothelial dysfunction, a significant predictor of hypertension clinically, require activation of the mineralocorticoid receptor in female mice. The clinical potential of this pathway remains under investigation; however, existing data indicate that a sex discrepancy exists in mechanisms of leptin-mediated hypertension between males and females and that leptin-stimulated aldosterone plays a significant role in females.

Topics: Aldosterone; Animals; Female; Gene Expression Regulation; Humans; Hypertension; Leptin; Male; Obesity; Sex Factors

The prevalence of overweight and obesity has increased significantly in the United States and worldwide. Among the many complications of obesity, hypertension is the most common and major one accounting for about 70% in the obese subjects. However, the pathophysiologic factors of obesity-related hypertension and its therapeutic options are not well understood at present. To better understand the pathophysiology of obesity-related hypertension and its treatment options, a Medline search of the English language literature was contacted between 2010 and 2018 and 22 pertinent papers were selected. The information from these papers together with collateral literature will be discussed in this review.

Topics: Adult; Animals; Body Mass Index; Dogs; Female; Humans; Hypertension; Leptin; Male; Mice; Middle Aged; Natriuretic Peptides; Obesity; Overweight; Prevalence; Renin-Angiotensin System; Sympathetic Nervous System; United States

Excessive adiposity raises blood pressure and accounts for 65-75% of primary hypertension, which is a major driver of cardiovascular and kidney diseases. In obesity, abnormal kidney function and associated increases in tubular sodium reabsorption initiate hypertension, which is often mild before the development of target organ injury. Factors that contribute to increased sodium reabsorption in obesity include kidney compression by visceral, perirenal and renal sinus fat; increased renal sympathetic nerve activity (RSNA); increased levels of anti-natriuretic hormones, such as angiotensin II and aldosterone; and adipokines, particularly leptin. The renal and neurohormonal pathways of obesity and hypertension are intertwined. For example, leptin increases RSNA by stimulating the central nervous system proopiomelanocortin-melanocortin 4 receptor pathway, and kidney compression and RSNA contribute to renin-angiotensin-aldosterone system activation. Glucocorticoids and/or oxidative stress may also contribute to mineralocorticoid receptor activation in obesity. Prolonged obesity and progressive renal injury often lead to the development of treatment-resistant hypertension. Patient management therefore often requires multiple antihypertensive drugs and concurrent treatment of dyslipidaemia, insulin resistance, diabetes and inflammation. If more effective strategies for the prevention and control of obesity are not developed, cardiorenal, metabolic and other obesity-associated diseases could overwhelm health-care systems in the future.

Topics: Adipokines; Aldosterone; Angiotensin II; Humans; Hypertension; Kidney; Kidney Tubules; Leptin; Obesity; Oxidative Stress; Pro-Opiomelanocortin; Receptor, Melanocortin, Type 4; Receptors, Mineralocorticoid; Renal Reabsorption; Renin; Sodium; Sympathetic Nervous System

Intrauterine growth restriction (IUGR) has been identified as a risk factor for adult chronic kidney disease (CKD), including hypertension (HTN). Accelerated postnatal catch-up growth superimposed to IUGR has been shown to further increase the risk of CKD and HTN. Although the impact of excessive postnatal growth without previous IUGR is less clear, excessive postnatal overfeeding in experimental animals shows a strong impact on the risk of CKD and HTN in adulthood. On the other hand, food restriction in the postnatal period seems to have a protective effect on CKD programming. All these effects are mediated at least partially by the activation of the renin-angiotensin system, leptin and neuropeptide Y (NPY) signaling and profibrotic pathways. Early nutrition, especially in the postnatal period has a significant impact on the risk of CKD and HTN at adulthood and should receive specific attention in the prevention of CKD and HTN.

Topics: Animals; Child Development; Disease Models, Animal; Fetal Growth Retardation; Humans; Hypertension; Infant Nutritional Physiological Phenomena; Infant, Low Birth Weight; Infant, Newborn; Leptin; Metabolic Networks and Pathways; Neuropeptide Y; Nutritional Status; Renal Insufficiency, Chronic; Renin-Angiotensin System

The major health issue of being overweight or obese relates to the development of hypertension, insulin resistance and diabetic complications. One of the major underlying factors influencing the elevated blood pressure in obesity is increased activity of the sympathetic nerves to particular organs such as the kidney.. There is now convincing evidence from animal studies that major signals such as leptin and insulin have a sympathoexcitatory action in the hypothalamus to cause hypertension. Recent studies suggest that this may involve 'neural plasticity' within hypothalamic signalling driven by central actions of leptin mediated via activation of melanocortin receptor signalling and activation of brain neurotrophic factors. This review describes the evidence to support the contribution of the SNS to obesity related hypertension and the major metabolic and adipokine signals.

Topics: Animals; Humans; Hypertension; Hypothalamus; Leptin; Obesity; Risk Factors; Signal Transduction; Sympathetic Nervous System

Despite the well-known global impact of overweight and obesity in the incidence of cerebrovascular disease, many aspects of this association are still inconsistently defined. In this chapter we aim to present a critical review on the links between obesity and both ischemic and hemorrhagic stroke and discuss its influence on functional outcomes, survival, and current treatments to acute and chronic stroke. The role of cerebrovascular endothelial function and respective modulation is also described as well as its laboratory and clinical assessment. In this context, the major contributing mechanisms underlying obesity-induced cerebral endothelial function (adipokine secretion, insulin resistance, inflammation, and hypertension) are discussed. A special emphasis is given to the participation of adipokines in the pathophysiology of stroke, namely adiponectin, leptin, resistin, apelin, and visfatin.

Topics: Adipokines; Adiponectin; Apelin; Brain Ischemia; Cerebrovascular Disorders; Endothelium, Vascular; Humans; Hypertension; Inflammation; Insulin Resistance; Intracranial Hemorrhages; Leptin; Nicotinamide Phosphoribosyltransferase; Obesity; Resistin; Stroke

Cardiovascular diseases (CVDs) are the number one cause of death globally. The risk for the development of CVDs is significantly increased in obesity. Leptin, the product of white adipose tissue, appears to contribute to the development of CVDs in obesity. Here, we discuss the premise that leptin engages the sympathetic nervous system and contributes to elevated blood pressure (BP) developing in obesity.. The long-term regulation of BP is dependent on the activity of the autonomic nervous system and specifically the sympathetic nervous system. Sympathetic nerve activity is significantly increased in obese rodents and humans. Leptin increases sympathetic nerve activity in rodents and humans; however, leptin only consistently increases BP chronically in rodents. The ability of leptin to increase BP in rodents is via both hypothalamic and extrahypothalamic regions. In leptin-deficient and leptin receptor-deficient humans, leptin appears to be the key reason for decreased systolic BP. However, in other research conducted in humans, chronic administration of leptin does not elevate BP.. Further research into the role of leptin in the development of CVDs, especially in humans, needs to be conducted.

Topics: Animals; Blood Pressure; Humans; Hypertension; Hypothalamus; Leptin; Obesity; Receptors, Leptin; Sympathetic Nervous System

Experimental and clinical studies have clearly shown the role of the sympathetic nervous system in the pathophysiology of several cardiovascular and non-cardiovascular diseases. This short review will be aimed at focusing and discussing the new information collected on two specific clinical conditions such as obesity and metabolic syndrome. The paper will briefly describe the four main mechanisms that represent the common link between these two pathophysiological conditions and that through the sympathetic nervous system contribute to increase the cardiovascular risk.

Topics: Animals; Baroreflex; Biomarkers; Blood Pressure; Cardiovascular System; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity, Abdominal; Oxidative Stress; Prognosis; Renin-Angiotensin System; Risk Factors; Sympathetic Nervous System

Obesity is a serious health hazard with rapidly increasing prevalence in the United States. In 2014, the World Health Organization estimated that nearly 2 billion people worldwide were overweight with an estimated 600 million of these obese. Obesity is associated with many chronic diseases, including cardiovascular disease and hypertension. Data from the Framingham Heart study suggest that approximately 78% of the risk for hypertension in men and 65% in women is related to excess body weight, a relationship that is further supported by studies showing increases in blood pressure with weight gain and decreases with weight loss. However, the exact mechanism by which excess body fat induces hypertension remains poorly understood. Several clinical studies have demonstrated elevated plasma aldosterone levels in obese individuals, especially those with visceral adiposity, with decreased aldosterone levels measured in concert with reduced blood pressure following weight loss. Since aldosterone is a mineralocorticoid hormone that regulates blood volume and pressure, serum aldosterone levels may link obesity and hypertension. Nevertheless, the mechanism by which obesity induces aldosterone production is unclear. A recent study by Belin de Chantemele and coworkers suggests that one adipose-released factor, leptin, is a direct agonist for aldosterone secretion; other adipose-related factors may also contribute to elevated aldosterone levels in obesity, such as very low-density lipoprotein (VLDL), the levels of which are elevated in obesity and which also directly stimulates aldosterone biosynthesis. This focused review explores the possible roles of leptin and VLDL in modulating aldosterone secretion to underlie obesity-associated hypertension.

Topics: Adipose Tissue; Aldosterone; Blood Pressure; Female; Humans; Hypertension; Leptin; Male; Obesity

The risk of hypertension is increased by intrauterine growth restriction (IUGR) and preterm birth. In the search for modifiable etiologies for this life-threatening cardiovascular morbidity, a number of pathways have been investigated, including excessive glucocorticoid exposure, nutritional deficiency and aberration in sex hormone levels. As a neurotrophic hormone that is intimately involved in the cardiovascular regulation and whose levels are influenced by glucocorticoids, nutritional status and sex hormones, leptin has emerged as a putative etiologic and thus a therapeutic agent. As a product of maternal and late fetal adipocytes and the placenta, circulating leptin typically surges late in gestation and declines after delivery until the infant consumes sufficient leptin-containing breast milk or accrues sufficient leptin-secreting adipose tissue to reestablish the circulating levels. The leptin deficiency seen in IUGR infants is a multifactorial manifestation of placental insufficiency, exaggerated glucocorticoid exposure and fetal adipose deficit. The preterm infant suffers from the same cascade of events, including separation from the placenta, antenatal steroid exposure and persistently underdeveloped adipose depots. Preterm infants remain leptin deficient beyond term gestation, rendering them susceptible to neurodevelopmental impairment and subsequent cardiovascular dysregulation. This pathologic pathway is efficiently modeled by placing neonatal mice into atypically large litters, thereby recapitulating the perinatal growth restriction-adult hypertension phenotype. In this model, neonatal leptin supplementation restores the physiologic leptin surge, attenuates the leptin-triggered sympathetic activation in adulthood and prevents leptin- or stress-evoked hypertension. Further pathway interrogation and clinical translation are needed to fully test the therapeutic potential of perinatal leptin supplementation.

Topics: Adiposity; Adult; Animals; Animals, Newborn; Disease Models, Animal; Female; Fetal Growth Retardation; Hormone Replacement Therapy; Humans; Hypertension; Hypothalamus; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Leptin; Male; Mice; Nerve Tissue Proteins; Neurodevelopmental Disorders; Pregnancy; Receptors, Leptin; Recombinant Proteins; Signal Transduction

Hypertension and associated cardiovascular diseases represent the most common health complication of obesity and the leading cause of morbidity and mortality in overweight and obese patients. Emerging evidence suggests a critical role for the central nervous system particularly the brain action of the adipocyte-derived hormone leptin in linking obesity and hypertension. The preserved ability of leptin to cause cardiovascular sympathetic nerve activation despite the resistance to the metabolic actions of the hormone appears essential in this pathological process. This review describes the evidence supporting the neurogenic bases for obesity-associated hypertension with a particular focus on the neuronal and molecular signaling pathways underlying leptin's effects on sympathetic nerve activity and blood pressure.

Topics: Adipocytes; Humans; Hypertension; Leptin; Obesity; Signal Transduction; Sympathetic Nervous System

The genes encoding adipose-derived hormone leptin and its receptor (LEPR) are increasingly deemed as hypertension-susceptibility genes. In this meta-analysis, we summarized the association of the II/I polymorphism in leptin gene and Gln223Arg polymorphism in LEPR gene with hypertension and circulating leptin.. PubMed and Embase were systematically searched. Data extraction and study quality were assessed in duplicate. Statistical analyses were carried out with the STATA software (v. 11.2).. A total of 11 articles written in English were eligible. Overall analysis identified a significant association between II/I polymorphism I allele and increased risk of hypertension under allelic (odds ratio; 95% confidence interval; P: 1.48; 1.06-2.08; 0.022) and homozygous genotypic (2.27; 1.20-4.29; 0.012) models. The magnitude of the association for II/I polymorphism I allele with hypertension was substantiated in Asians and for essential hypertension under both genetic models. Overall and subgroup analyses failed to reveal any significance for the association between the Gln223Arg polymorphism and hypertension risk. Carriers of Gln223Arg polymorphism Gln/Gln genotype had significantly higher circulating leptin than the Arg/Arg genotype carriers (weighted mean difference; 95% confidence interval; P: 1.61 ng/mL; 0.02-3.20; 0.047), and this significance persisted in essential hypertension subgroup (1.69 ng/mL; 0.02-3.35; 0.047). There were low probabilities of publication bias for the above comparisons.. Our findings support the contributory role of the II/I polymorphism in leptin gene in the pathogenesis of hypertension, and this role was more evident in Asians and for essential hypertension.

Topics: Alleles; Asian People; Essential Hypertension; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Leptin; Obesity; Odds Ratio; Polymorphism, Single Nucleotide; Receptors, Leptin; White People

Adipokines are hormones produced by adipocytes and have been involved in multiple pathologic pathways, including inflammatory and cardiovascular complications in essential hypertension. Arterial stiffness is a frequent vascular complication that represents increased cardiovascular risk in hypertensive patients. Adipokines, such as adiponectin, leptin and resistin, might be implicated in hypertension, as well as in vascular alterations associated with this condition. Arterial stiffness has proven to be a predictor of cardiovascular events. Obesity and target-organ damage such as arterial stiffness are features associated with hypertension. This review aims to update the association between adipokines and arterial stiffness in essential and resistant hypertension (RHTN).

Topics: Adipocytes; Adipokines; Adiponectin; Essential Hypertension; Humans; Hypertension; Leptin; Obesity; Resistin; Risk Factors; Vascular Stiffness

Several articles have dealt with the importance and mechanisms of the sympathetic nervous system alterations in experimental animal models of hypertension. This review addresses the role of the sympathetic nervous system in the pathophysiology and therapy of human hypertension. We first discuss the strengths and limitations of various techniques for assessing the sympathetic nervous system in humans, with a focus on heart rate, plasma norepinephrine, microneurographic recording of sympathetic nerve traffic, and measurements of radiolabeled norepinephrine spillover. We then examine the evidence supporting the importance of neuroadrenergic factors as promoters and amplifiers of human hypertension. We expand on the role of the sympathetic nervous system in 2 increasingly common forms of secondary hypertension, namely hypertension associated with obesity and with renal disease. With this background, we examine interventions of sympathetic deactivation as a mode of antihypertensive treatment. Particular emphasis is given to the background and results of recent therapeutic approaches based on carotid baroreceptor stimulation and radiofrequency ablation of the renal nerves.

Topics: Animals; Antihypertensive Agents; Clinical Trials as Topic; Diagnostic Techniques, Cardiovascular; Forecasting; Heart Rate; Humans; Hyperinsulinism; Hypertension; Hypertension, Renal; Insulin Resistance; Kidney; Kidney Diseases; Leptin; Melanocortins; Metabolic Syndrome; Multicenter Studies as Topic; Neuroimaging; Norepinephrine; Obesity; Sympathectomy; Sympathetic Fibers, Postganglionic; Sympathetic Nervous System; Vasoconstriction

Excess weight gain, especially when associated with increased visceral adiposity, is a major cause of hypertension, accounting for 65% to 75% of the risk for human primary (essential) hypertension. Increased renal tubular sodium reabsorption impairs pressure natriuresis and plays an important role in initiating obesity hypertension. The mediators of abnormal kidney function and increased blood pressure during development of obesity hypertension include (1) physical compression of the kidneys by fat in and around the kidneys, (2) activation of the renin-angiotensin-aldosterone system, and (3) increased sympathetic nervous system activity. Activation of the renin-angiotensin-aldosterone system is likely due, in part, to renal compression, as well as sympathetic nervous system activation. However, obesity also causes mineralocorticoid receptor activation independent of aldosterone or angiotensin II. The mechanisms for sympathetic nervous system activation in obesity have not been fully elucidated but may require leptin and activation of the brain melanocortin system. With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation. Unless effective antiobesity drugs are developed, the effect of obesity on hypertension and related cardiovascular, renal and metabolic disorders is likely to become even more important in the future as the prevalence of obesity continues to increase.

Topics: Aldosterone; Animals; Antihypertensive Agents; Dyslipidemias; Heart Conduction System; Hemodynamics; Humans; Hypertension; Insulin Resistance; Intra-Abdominal Fat; Kidney; Leptin; Metabolic Syndrome; Models, Animal; Models, Cardiovascular; Natriuresis; Obesity; Organ Specificity; Parasympathetic Nervous System; Pressure; Prevalence; Pro-Opiomelanocortin; Receptors, Leptin; Renal Insufficiency, Chronic; Renin-Angiotensin System; Sodium; Sympathetic Nervous System

Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential genetic and racial differences or environmental factors that may protect obese patients against the development of hypertension and other co-morbidities. Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of α-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity. Furthermore, gene-environment interactions may have the potential to modify gene expression and epigenetic mechanisms could also contribute to the heritability of obesity-induced hypertension. Finally, differences in nutrition, gut microbiota, exposure to sun light and exercise may play an important role in the presence or absence of hypertension in obesity.

Topics: Animals; Appetite; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Exercise; Gene-Environment Interaction; Humans; Hypertension; Leptin; Obesity; Potassium, Dietary; Protective Factors; Receptor, Melanocortin, Type 4; Sodium, Dietary; Sympathetic Nervous System

Leptin is a protein hormone produced mainly by obese gene and secreted by adipose tissue and exerts the biological effects through leptin receptors. With the progress in research on the function and receptor signal transduction related leptin and leptin resistance, it has been found that leptin is associated with the development and progression of many cardiovascular diseases, such as hypertension and left ventricular hypertrophy. Some studies have reported that leptin resistance is the pathologic basis for a variety of cardiovascular diseases. This paper will briefly review the advances in the study of correlation between leptin and hypertensive-left ventricular hypertrophy (HLVH), focusing on the relationship between leptin and various factors related to HLVH, such as sympathetic nervous system, renin angiotensin aldosterone system, growth factors, inflammatory factors and insulin resistance.. 瘦素是主要由肥胖基因编码、脂肪组织分泌的一种蛋白质类激素，通过作用于瘦素受体发挥其生物学效应。随着对瘦素功能、瘦素受体信号转导及瘦素抵抗等方面研究的深入，发现瘦素与许多心血管疾病，尤其与高血压的发生、发展密切相关。左心室肥厚(left ventricular hypertrophy，LVH)是高血压最常见的并发症之一。瘦素与促进高血压LVH形成的各种因素如交感神经系统、肾素-血管紧张素-醛固酮系统、生长因子、炎症细胞因子及胰岛素抵抗有密切关系。.

Topics: Adipose Tissue; Cardiovascular Diseases; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin Resistance; Leptin; Receptors, Leptin; Renin-Angiotensin System; Sympathetic Nervous System

Links between short sleep duration and obesity, type 2 diabetes, hypertension, and cardiovascular disease may be mediated through changes in dietary intake. This review provides an overview of recent epidemiologic studies on the relations between habitual short sleep duration and dietary intake in adults from 16 cross-sectional studies. The studies have observed consistent associations between short sleep duration and higher total energy intake and higher total fat intake, and limited evidence for lower fruit intake, and lower quality diets. Evidence also suggests that short sleepers may have irregular eating behavior deviating from the traditional 3 meals/d to fewer main meals and more frequent, smaller, energy-dense, and highly palatable snacks at night. Although the impact of short sleep duration on dietary intake tends to be small, if chronic, it may contribute to an increased risk of obesity and related chronic disease. Mechanisms mediating the associations between sleep duration and dietary intake are likely to be multifactorial and include differences in the appetite-related hormones leptin and ghrelin, hedonic pathways, extended hours for intake, and altered time of intake. Taking into account these epidemiologic relations and the evidence for causal relations between sleep loss and metabolism and cardiovascular function, health promotion strategies should emphasize improved sleep as an additional factor in health and weight management. Moreover, future sleep interventions in controlled studies and sleep extension trials in chronic short sleepers are imperative for establishing whether there is a causal relation between short sleep duration and changes in dietary intake.

Topics: Adult; Aged; Cardiovascular Diseases; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Diet; Dietary Fats; Dietary Fiber; Energy Intake; Feeding Behavior; Female; Fruit; Ghrelin; Health Promotion; Health Status; Humans; Hypertension; Leptin; Male; Middle Aged; Nutritive Value; Obesity; Sleep; Sleep Deprivation; Snacks; Time Factors

Leptin is a 16-kDa peptide hormone that is primarily synthesized and secreted by adipose tissue. One of the major actions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake, elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect mechanisms, may play an important role in cardiovascular and renal regulation. Although the relevance of endogenous leptin needs further clarification, it appears to function as a pressure- and volume-regulating factor under conditions of health. However, in abnormal situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for direct renal, vascular and cardiac damage.

Topics: Animals; Humans; Hypertension; Leptin; Neurosecretory Systems; Obesity

Mother-child cohort studies have established that both pre-pregnancy body mass index (BMI) and gestational weight gain are independently associated with cardio-metabolic risk factors in young adult offspring, including systolic and diastolic blood pressure. Animal models in sheep and non-human primates provide further evidence for the influence of maternal obesity on offspring cardiovascular function, whilst recent studies in rodents suggest that perinatal exposure to the metabolic milieu of maternal obesity may permanently change the central regulatory pathways involved in blood pressure regulation. Leptin plays an important role in the central control of appetite, is also involved in activation of efferent sympathetic pathways to both thermogenic and non-thermogenic tissues, such as the kidney, and is therefore implicated in obesity-related hypertension. Leptin is also thought to have a neurotrophic role in the development of the hypothalamus, and altered neonatal leptin profiles secondary to maternal obesity are associated with permanently altered hypothalamic structure and function. In rodent studies, maternal obesity confers persistent sympathoexcitatory hyper-responsiveness and hypertension acquired in the early stages of development. Experimental neonatal hyperleptinaemia in naive rat pups provides further evidence of heightened sympathetic tone and proof of principle that hyperleptinaemia during a critical window of hypothalamic development may directly lead to adulthood hypertension. Insight from these animal models raises the possibility that early-life exposure to leptin in humans may lead to early onset essential hypertension. Ongoing mother-child cohort and intervention studies in obese pregnant women provide a unique opportunity to address associations between maternal obesity and offspring cardiovascular function. The goal of the review is to highlight the potential importance of leptin in the developmental programming of hypertension in obese pregnancy.

Topics: Animals; Female; Humans; Hypertension; Leptin; Mothers; Obesity; Pregnancy; Prenatal Exposure Delayed Effects

Resistant hypertension in diabetes is associated with poor cardiovascular and renal outcomes. This brief review will examine the definitions and epidemiology of resistant hypertension and consider the differences between apparent resistant hypertension and truly resistant or refractory hypertension. It will review the role of the sympathetic nervous system in resistant hypertension. It will consider the relationship between obesity and leptin resistance and sympathetic signaling; the role of obstructive sleep apnea in resistant hypertension; and the role of aldosterone in resistant hypertension. It will conclude by mentioning briefly renal nerve ablation.

Topics: Aldosterone; Diabetes Mellitus; Humans; Hypertension; Leptin; Obesity; Sympathetic Nervous System

White adipose tissue secretes a large variety of compounds named adipokines amongst which, leptin exhibits pleiotropic metabolic actions. Leptin is an anorexigenic hormone, secreted in proportion of fat mass, with additional effects on the regulation of inflammation, cardiovascular system, immunity, hematopoiesis and bone metabolism. Chronic kidney disease (CKD) is characterized by an increase of plasma leptin concentration that may be explained by a lack of renal clearance. Hyperleptinemia plays a key role in the pathogenesis of complications associated with CKD such as cachexia, protein energy wasting, chronic inflammation, insulin resistance, cardiovascular damages and bone complications. Leptin is also involved in the progression of renal disease through its pro-fibrotic and pro-hypertensive actions. Most of the adverse effects of leptin have been documented both experimentally and clinically. Leptin may therefore be considered as an uremic toxin in CKD. The aim of this review is to summarize the pathophysiological and clinical role of leptin in in vitro studies, experimental models, as well as in patients suffering from CKD.

Topics: Adipose Tissue; Cachexia; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Receptors, Leptin; Renal Insufficiency, Chronic; Toxins, Biological

Resistant hypertension (RH) is a multifactorial disease, frequently associated with obesity and characterized by blood pressure above goal (140/90 mm Hg) despite the concurrent use of ≥3 antihypertensive drugs of different classes. The mechanisms of obesity-related hypertension include, among others, aldosterone excess and inflammatory adipokines, which have demonstrated a significant role in the pathogenesis of metabolic syndrome and RH. This review aims to summarize recent studies on the role of the adipokines leptin, resistin, and adiponectin in the pathophysiology of RH and target-organ damage associated with this condition. The deregulation of adipokine levels has been associated with clinical characteristics frequently recognized in RH such as diabetes, hyperactivity of sympathetic and renin-angiotensin-aldosterone systems, and vascular and renal damage. Strategies to regulate adipokines may be promising for the management of RH and some clinical implications must be considered when managing controlled and uncontrolled patients with RH.

Topics: Adipokines; Adiponectin; Antihypertensive Agents; Drug Resistance; Drug Therapy, Combination; Humans; Hypertension; Leptin; Obesity; Resistin

Although obesity is a well-known risk factor for hypertension, the mechanisms by which hypertension develops in obese patients are not entirely clear. Animal models of obesity and their different susceptibilities to develop hypertension have revealed some of the mechanisms linking obesity and hypertension. Adipose tissue is an endocrine organ secreting hormones that impact blood pressure, such as elements of the renin-angiotensin system whose role in hypertension have been established. In addition, the appetite-suppressing adipokine leptin activates the sympathetic nervous system via the melanocortin system, and this activation, especially in the kidney, increases blood pressure. Leptin secretion from adipocytes is increased in most models of obesity due to leptin resistance, although the resistance is often selective to the anorexigenic effect, while the susceptibility to the hypertensive effect remains intact. Understanding the pathways by which obesity contributes to increased blood pressure will hopefully pave the way to and better define the appropriate treatment for obesity-induced hypertension.

Topics: Animals; Blood Pressure; Disease Models, Animal; Humans; Hypertension; Leptin; Obesity; Renin-Angiotensin System

Obesity is recognized as a major worldwide health problem. Excess weight gain is the most common cause of elevated blood pressure (BP) and markedly increases the risk of metabolic, cardiovascular and renal diseases. Although the mechanisms linking obesity with hypertension have not been fully elucidated, increased sympathetic nervous system (SNS) activity contributes to elevated BP in obese subjects. Recent evidence indicates that leptin and the central nervous system (CNS) melanocortin system, including melanocortin 4 receptors (MC4R), play a key role in linking obesity with increased SNS activity and hypertension. Leptin, a peptide-hormone produced by adipose tissue, crosses the blood-brain barrier and activates brain centers that control multiple metabolic functions as well as SNS activity and BP via the CNS melanocortin system. The crosstalk between peripheral signals (e.g., leptin) and activation of CNS pathways (e.g., MC4R) that regulate energy balance, SNS activity and BP represents an important target for treating obesity and its metabolic and cardiovascular consequences.

Topics: Animals; Appetite; Blood Pressure; Humans; Hypertension; Leptin; Obesity; Receptor, Melanocortin, Type 4; Receptors, Leptin; Sympathetic Nervous System

Adipose tissue can be considered as a huge gland producing paracrine and endocrine hormones, the adipo(cyto)kines. There is growing evidence that these adipo(cyto)kines may link obesity to cardiovascular diseases. The excessive adipocyte hypertrophy in obesity induces hypoxia in adipose tissue. This leads to adiposopathy, the process that converts "healthy" adipose tissue to "sick" adipose tissue. This is accompanied by a change in profile of adipo(cyto)kines released, with less production of the "healthy" adipo(cyto)kines such as adiponectin and omentin and more release of the "unhealthy" adipo(cyto)kines, ultimately leading to the development of cardiovascular diseases. The present review provides a concise and general overview of the actual concepts of the role of adipo(cyto)kines in endothelial dysfunction, hypertension, atherosclerosis and heart diseases. The knowledge of these concepts may lead to new tools to improve health in the next generations.

Topics: Adipocytes; Adipokines; Adiponectin; Adipose Tissue; Animals; Atherosclerosis; Body Mass Index; Cardiovascular Diseases; Cell Hypoxia; Endothelium-Dependent Relaxing Factors; Endothelium, Vascular; Heart Diseases; Humans; Hypertension; Leptin; Obesity; Renin-Angiotensin System; Resistin

In addition to effects on appetite and metabolism, leptin influences many neuroendocrine and physiological systems, including the sympathetic nervous system. Building on my Carl Ludwig Lecture of the American Physiological Society, I review the sympathetic and cardiovascular actions of leptin. The review focuses on a critical analysis of the concept of selective leptin resistance (SLR) and the role of leptin in the pathogenesis of obesity-induced hypertension in both experimental animals and humans. We introduced the concept of SLR in 2002 to explain how leptin might increase blood pressure (BP) in obese states, such as diet-induced obesity (DIO), that are accompanied by partial leptin resistance. This concept, analogous to selective insulin resistance in the metabolic syndrome, holds that in several genetic and acquired models of obesity, there is preservation of the renal sympathetic and pressor actions of leptin despite attenuation of the appetite and weight-reducing actions. Two potential overlapping mechanisms of SLR are reviewed: 1) differential leptin molecular signaling pathways that mediate selective as opposed to universal leptin action and 2) brain site-specific leptin action and resistance. Although the phenomenon of SLR in DIO has so far focused on preservation of sympathetic and BP actions of leptin, consideration should be given to the possibility that this concept may extend to preservation of other actions of leptin. Finally, I review perplexing data on the effects of leptin on sympathetic activity and BP in humans and its role in human obesity-induced hypertension.

Topics: Animals; Brain; Humans; Hypertension; Leptin; Myocardium; Obesity; Sympathetic Nervous System

Osteoporosis is a high-prevalence disease, particularly in developed countries, and results in high costs both to the individual and to society through associated fragility fractures. There is an urgent need for identification of novel drug targets and development of new anti-osteoporotic agents. Between 30 and 80% of osteoporotic fractures cannot be prevented despite current treatments achieving relative fracture risk reduction of up to 20%, 50%, and 70% for non-vertebral, hip and spine fractures, respectively. Traditionally, the decline in gonadal hormones has been studied as the sole hormonal determinant for the loss of bone mineral density in osteoporosis. However, recent studies have identified receptors for numerous non-gonadal hormones such as PTH, angiotensin II, leptin, adiponectin, insulin and insulin-like growth factor-1 on the osteoblast lineage cells that directly regulate bone turnover. These hormones are also involved in the pathogenesis of metabolic syndrome risk factors, particularly hypertension, type-II diabetes and obesity. By activating their respective receptors on osteoblastic lineage cells, these hormones appear to act through a common mechanism by down-regulating receptors for activation of nuclear factor kappa B ligand (RANKL) and up-regulating osteoprotegerin (OPG) with inverse responses for adiponectin. Receptors for amylin, gastric inhibitory polypeptide and ghrelin and have also been identified on the osteoblast lineage cells although the roles of these receptors in bone turnover are controversial or poorly studied. Moreover, bone turnover may be independently regulated by modulation of osteoclast-osteoblast function and bone marrow adiposity. Leptin appears to be the only hormone that is a known regulator of both bone mineralisation and bone adiposity.

Topics: Adiposity; Animals; Bone Remodeling; Hormones; Humans; Hyperglycemia; Hypertension; Leptin; Osteoclasts; Osteoporosis; Parathyroid Hormone; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cell Surface; Signal Transduction

Obesity is a major worldwide health problem. Excess weight gain is the most significant preventable cause of increased blood pressure (BP) in patients with essential hypertension and increases the risk for cardiovascular and renal diseases. Our goal is to review the mechanisms that link obesity with hypertension, with special emphasis on the role of leptin and the brain melanocortin system in driving sympathetic activation in obesity.. Despite increased interest in obesity as a major risk for developing hypertension, the precise mechanisms linking excess weight gain with increases in BP are still elusive. Current evidence suggests that increased sympathetic nervous system (SNS) activity contributes to impaired renal-pressure natriuresis and sodium retention in obesity. Recent findings indicate that the adipocyte-derived hormone, leptin, activates brain centers that regulate SNS activity through a melanocortin-system-dependent pathway. The interaction of leptin and the brain melanocortin system represents an important area of research to further our understanding of the mechanisms leading to sympathetic activation in obesity.. Sympathetic overactivity is an important link between excess weight gain and increased BP. Hormones and cytokines secreted by the adipose tissue that interact with neural pathways (e.g. melanocortin system) appear to play a key role in contributing to sympathetic activation in obesity and represent potential new targets for therapies.

Topics: Adipocytes; Animals; Blood Pressure; Central Nervous System; Humans; Hypertension; Leptin; Melanocortins; Obesity; Receptor, Melanocortin, Type 4; Signal Transduction; Sympathetic Nervous System; Weight Gain

The number of obese or overweight humans continues to increase worldwide. Hypertension is a serious disease that often develops in obesity, but it is not clear how obesity increases the risk of hypertension. However, both obesity and hypertension increase the risk of cardiovascular diseases (CVD). In this review, we examine how obesity may increase the risk of developing hypertension. Specifically, we discuss how the adipose-derived hormone leptin influences the sympathetic nervous system (SNS), through actions in the brain to elevate energy expenditure (EE) while also contributing to hypertension in obesity.

Topics: Brain; Energy Metabolism; Humans; Hypertension; Leptin; Obesity

Obesity and the accompanying metabolic syndrome are among the most important causes of cardiovascular pathologies associated with endothelial dysfunction, such as arterial hypertension and atherosclerosis. This detrimental effect of obesity is mediated, in part, by excessive production of the adipose tissue hormone leptin. Under physiological conditions leptin induces endothelium-dependent vasorelaxation by stimulating nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF). Leptin activates endothelial NO synthase (eNOS) through a mechanism involving AMP-activated protein kinase (AMPK) and protein kinase B/Akt, which phosphorylates eNOS at Ser(1177) , increasing its activity. Under pathological conditions, such as obesity and metabolic syndrome, the NO-mediated vasodilatory effect of leptin is impaired. Resistance to the acute NO-mimetic effect of leptin is accounted for by chronic hyperleptinaemia and may result from different mechanisms, such as downregulation of leptin receptors, increased levels of circulating C-reactive protein, oxidative stress and overexpression of suppressor of cytokine signalling-3. In short-lasting obesity, impaired leptin-induced NO production is compensated by EDHF; however, in advanced metabolic syndrome, the contribution of EDHF to the haemodynamic effect of leptin becomes inefficient. Resistance to the vasodilatory effects of leptin may contribute to the development of arterial hypertension owing to unopposed stimulation of the sympathetic nervous system by this hormone.

Topics: Animals; Blood Pressure; Endothelium, Vascular; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Vasodilation

Obesity markedly increases the risk of hypertension and cardiovascular disease, which may be related to activation of the sympathetic nervous system (SNS). Sympathetic overactivity directly and indirectly contributes to blood pressure (BP) elevation in obesity, including stimulation of the renin-angiotensin-aldosterone system (RAAS). The adipocyte-derived peptide leptin suppresses appetite, increases thermogenesis, but also raises SNS activity and BP. Obese individuals exhibit hyperleptinemia but are resistant to its appetite-suppressing actions. Interestingly, animal models of obesity exhibit preserved sympathoexcitatory and pressor actions of leptin, despite resistance to its anorexic and metabolic actions, suggesting selective leptin resistance. Disturbance of intracellular signaling at specific hypothalamic neural networks appears to underlie selective leptin resistance. Delineation of these pathways should lead to novel approaches to treatment. In the meantime, treatment of obesity-hypertension has relied on antihypertensive drugs. Although sympathetic blockade is mechanistically attractive in obesity-hypertension, in practice its effects are disappointing because of adverse metabolic effects and inferior outcomes. On the basis of subgroup analyses of obese patients in large randomized clinical trials, drugs such as diuretics and RAAS blockers appear superior in preventing cardiovascular events in obesity--hypertension. An underused alternative approach to obesity-hypertension is induction of weight loss, which reduces circulating leptin and insulin, partially reverses resistance to these hormones, decreases sympathetic activation and improves BP and other risk factors. Though weight loss induced by lifestyle is often modest and transient, carefully selected pharmacological weight loss therapies can produce substantial and sustained antihypertensive effects additive to lifestyle interventions.

Topics: Humans; Hypertension; Leptin; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Weight Loss

Obesity is now recognised as one of the most important risk factors for heart disease. Obese individuals have high circulating levels of leptin, a hormone secreted by adipose tissue and involved in energy homeostasis. Growing evidence suggests that leptin may contribute to the development of cardiac dysfunction. In a large prospective study leptin has been shown to be an independent risk factor for coronary heart disease. An independent positive association has also been found between plasma leptin levels and heart rate in hypertensive patients and heart transplant recipients. In animal studies chronic leptin infusion increased heart rate and blood pressure. It has also been demonstrated that circulating leptin levels are elevated in patients with heart failure. The level of plasma leptin was associated with increased myocardial wall thickness and correlated with left ventricular mass, suggesting a role for this hormone in mediating left ventricular hypertrophy in humans. Moreover, leptin directly induced hypertrophy and hyperplasia in human and rodent cardiomyocytes, accompanied by cardiac extracellular matrix remodelling. Leptin may also influence energy substrate utilisation in cardiac tissue. These findings suggest that leptin acting directly or through the sympathetic nervous system may have adverse effects on cardiac structure and function, and that chronic hyperleptinaemia may greatly increase the risk of cardiac disorders. Additional studies are needed to define the role of leptin in cardiac physiology and pathophysiology, nevertheless the reduction in plasma leptin levels with caloric restriction and weight loss may prevent cardiac dysfunction in obese patients.

Topics: Adipose Tissue; Cardiovascular Diseases; Coronary Artery Disease; Heart Rate; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Myocardium; Myocytes, Cardiac; Obesity; Ventricular Remodeling; Weight Loss

Since the initial identification of leptin as the product of the ob gene in 1994, the signaling pathways by which this hormone alters cell physiology have been the subject of extensive investigations. The fact that leptin can induce nitric oxide (NO) production was first demonstrated in studies of the pituitary gland and pancreatic islets. A large number of additional studies further showed that this adipokine stimulates NO synthesis in multiple tissues. This review article discusses the role of leptin in NO production and its pathophysiological consequences. The role of this gaseous messenger in cell physiology depends on the cell type, the concentration of NO and the duration of exposure. It can be either a potent oxidant or a protector of cell integrity against the formation of reactive oxygen species. Leptin plays two opposing roles on arterial pressure. It exerts a hypertensive effect due to sympathetic activation and a vasorelaxant effect due to NO production. This adipokine acts via NO to produce pro-inflammatory factors in cartilage pathology, potentially contributing to an increased risk for osteoarthritis. Another well-documented role of leptin-induced NO, acting either directly or via the hypothalamus, concerns lipid metabolism in muscle and adipose tissue. In adipocytes, the direct and rapid action of leptin is to activate the nitric oxide synthase III, which favors lipolysis. In contrast, in the long-term, leptin reduces lipolysis. However, both in the short-term and in the long-term, glyceroneogenesis and its key enzyme, the cytosolic phosphoenolpyruvatecarboxykinase (PEPCK-C), are down-regulated by the adipokine, thus favoring fatty acid release. Hence, leptin-induced NO production plays a crucial role in fatty acid metabolism in adipose tissue. The resulting effects are to prevent lipid storage and to improve energy expenditure, with possible improvements of the obese state and its associated diseases.

Topics: Animals; Blood Vessels; Glucose; Humans; Hypertension; Leptin; Lipid Metabolism; Nitric Oxide

Adipose tissue is now considered to be an active physiologic system operating in concert with multiple other organs. Leptin is a peptide hormone that is primarily synthesized and secreted by adipose tissue whose principal action is the control of appetite and energy balance. However, current information suggests that leptin exerts pleiotropic effects on several organ systems. Herein, we review the potential role of leptin in cardiovascular and renal physiological conditions as well as pathophysiological situations including obesity and hypertension.. Increasing evidence suggests that leptin may function as a pressure and volume-regulating factor under conditions of health; however, in situations characterized by chronic hyperleptinemia such as obesity, it may function pathophysiologically for the development of hypertension and possibly also for adverse renal, vascular and cardiac remodeling.. Adipose tissue should be regarded as a potentially important mediator of cardiorenal physiology. Further research awaits the characterization of additional mechanisms of action of leptin, including its interface with other important endocrine and hemodynamic sodium-volume regulatory systems, in both health and disease, particularly in obesity and related comorbidities. This information could lead to the development of leptin analogues as well as leptin receptor blockers that given specific circumstances could optimize the beneficial actions of the hormone and minimize its deleterious effects.

Topics: Adipose Tissue; Animals; Blood Pressure; Cardiovascular Diseases; Cardiovascular System; Homeostasis; Humans; Hypertension; Kidney; Leptin; Models, Biological; Models, Cardiovascular; Obesity; Receptors, Leptin; Renal Insufficiency, Chronic; Water-Electrolyte Balance

Obesity is a universal health problem of increasing prevalence and represents a major public health concern. Obesity is associated with a high risk of developing cardiovascular and metabolic diseases such as hypertension, coronary atherosclerosis, myocardial hypertrophy, diabetes, dyslipidemia, and increased cardiovascular morbidity and mortality. There has been an ongoing search for mediators between obesity and cardiovascular disease. Leptin is a novel and very promising molecule of research that may link these pathologic conditions. Since its discovery in 1994, major advances have been made in the understanding of neuroendocrine mechanisms regulating appetite, metabolism, adiposity, sympathetic tone and blood pressure. In this review, we discuss the physiological and pathophysiological roles of leptin in the causation of various cardiovascular diseases.

Topics: Cardiovascular Diseases; Diabetes Mellitus; Homeostasis; Humans; Hypertension; Leptin; Obesity; Risk Factors

A wealth of investigations, ranging from clinical and animal model studies to in vitro analyses, have generated great interest in the cardiovascular effects of leptin. Accordingly, many studies have examined the contribution of leptin to cardiac remodeling in heart failure and whether the effects of leptin on metabolism, apoptosis, extracellular matrix remodeling, and hypertrophy could explain the so-called obesity paradox. Furthermore, obesity and hyperleptinemia have often been associated with hypertension, and regulation of sympathetic tone or direct effects of leptin on contributors such as atherosclerosis, endothelial dysfunction, and thrombosis have been documented. Unfortunately, translating basic research studies in vitro, or in animal models, to human physiology has proven difficult. The degree of leptin resistance in obesity is one intriguing issue that must be resolved. Furthermore, the importance of autocrine and paracrine effects of leptin derived from the heart and perivascular adipose tissue must be further studied. Carefully planned and executed research to conclusively establish distinct effects of leptin on the cardiovascular system in normal and diseased states will be essential to harness any therapeutic potential associated with leptin's effects.

Topics: Adipose Tissue; Animals; Apoptosis; Atherosclerosis; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Endothelium, Vascular; Extracellular Matrix; Humans; Hypertension; Inflammation; Leptin; Myocardium; Obesity

Excess weight gain contributes to increased blood pressure in most patients with essential hypertension. Although the mechanisms of obesity hypertension are not fully understood, increased renal sodium reabsorption and impaired pressure natriuresis play key roles. Several mechanisms contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system, which appears to be mediated in part by increased levels of the adipocyte-derived hormone leptin, stimulation of pro-opiomelanocortin neurons, and subsequent activation of central nervous system melanocortin 4 receptors.

Topics: Adipocytes; Adipose Tissue; Animals; Body Weight; Humans; Hypertension; Kidney; Leptin; Melanocortins; Mice; Models, Biological; Neurons; Obesity; Pro-Opiomelanocortin; Rats; Receptor, Melanocortin, Type 4; Sympathetic Nervous System

The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle of infinite feedback gain, seems to be shifted toward higher blood-pressure levels in obese individuals. During the early phases of obesity, primary sodium retention exists as a result of increase in renal tubular reabsorption. Extracellular-fluid volume is expanded and the kidney-fluid apparatus is resetted to a hypertensive level, consistent with a model of hypertension because of volume overload. Plasma renin activity, angiotensinogen, angiotensin II and aldosterone values display significant increase during obesity. Insulin resistance and inflammation may promote an altered profile of vascular function and consequently hypertension. Leptin and other neuropeptides are possible links between obesity and the development of hypertension. Obesity should be considered as a chronic medical condition, which is likely to require long-term treatment. Understanding of the mechanisms associated with obesity-related hypertension is essential for successful treatment strategies.

Topics: Blood Pressure; Humans; Hypertension; Insulin Resistance; Leptin; Natriuresis; Obesity; Sympathetic Nervous System

Obstructive sleep apnea (OSA) is a chronic disease characterized by repetitive partial or complete closure of the upper airway during sleep. OSA tends to be associated with components of metabolic syndrome sharing a common ground of metabolic changes with metabolic syndrome itself. Recent studies showed that subjects with OSA were 6-9 times more likely to have metabolic syndrome than subjects without OSA. Intermittent hypoxia and sleep fragmentation in OSA can initiate intermediary mechanisms (oxidative stress, neurohumoral changes, inflammation) leading to the components of metabolic syndrome. OSA has been suggested to be a novel risk factor, inside the metabolic syndrome, contributing to increased cardiovascular risk. Several studies report that continuous positive airway pressure (CPAP) treatment can reverse pathophysiological changes in OSA, increasing insulin sensitivity and reducing blood pressure. Recent evidences show that CPAP treatment reduces the risk of cardiovascular events and mortality in subjects with OSA. Some subjects with metabolic syndrome can be affected by undiagnosed OSA: CPAP treatment could significantly reduce cardiovascular risk in this subgroup of patients.

Topics: Age Factors; Aged; Blood Glucose; Cardiovascular Diseases; Clinical Trials as Topic; Continuous Positive Airway Pressure; Death, Sudden, Cardiac; Diabetes Mellitus, Type 2; Glucose Tolerance Test; Humans; Hypertension; Insulin Resistance; Leptin; MEDLINE; Metabolic Syndrome; Obesity; Randomized Controlled Trials as Topic; Risk Factors; Sleep Apnea, Obstructive; Stroke

Obesity is characterized by increased concentration of leptin and disturbance of the feedback between hyperleptinaemia and enhanced appetite. The hyperleptinaemia is often combined with hyperglycaemia and arterial hypertension and seems to be a predictor of acute cardiovascular events. Leptin inhibitors might be used in the future for therapy in case of the metabolic syndrome.

Topics: Animals; Appetite; Humans; Hyperglycemia; Hypertension; Leptin; Metabolic Syndrome

Obesity is a major risk factor for hypertension. Adipose tissue releases numerous substances that act on the pathophysiologic mechanisms of blood pressure. Management of obese patients with high blood pressure includes weight loss efforts, but antihypertensive treatment is most often necessary. Beta-blockers, alone or with thiazide diuretics, increase the risk of diabetes in hypertensive patients. Treatment against hypertension must include a renin-angiotensin system blocker, with a calcium channel blocker or a thiazide diuretic, if necessary.

Topics: Adiponectin; Adipose Tissue; Antihypertensive Agents; Blood Pressure; Combined Modality Therapy; Humans; Hypertension; Insulin Resistance; Leptin; Obesity; Sympathetic Nervous System; Weight Loss

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Diabetes Mellitus; Drug Therapy, Combination; Humans; Hypertension; Insulin Resistance; Leptin; Obesity

The epidemic of obesity in the United States and around the world is intensifying in severity and scope and has been implicated as an underlying mechanism in systemic hypertension. Obese hypertensive individuals characteristically exhibit volume congestion, relative elevation in heart rate, and high cardiac output with concomitant activation of the renin-angiotensin-aldosterone system. When the metabolic syndrome is present, insulin resistance and hyperinsulinemia may contribute to hypertension through diverse mechanisms. Blood pressure can be lowered when weight control measures are successful, using, for example, caloric restriction, aerobic exercise, weight loss drugs, or bariatric surgery. A major clinical challenge resides in converting short-term weight reduction into a sustained benefit. Pharmacotherapy for the obese hypertensive patient may require multiple agents, with an optimal regimen consisting of inhibitors of the renin-angiotensin-aldosterone system, thiazide diuretics, beta-blockers, and calcium channel blockers if needed to attain contemporary blood pressure treatment goals.

Topics: Antihypertensive Agents; Bariatric Surgery; Blood Pressure; Drug Therapy, Combination; Hemodynamics; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Renin-Angiotensin System; Risk Reduction Behavior; Sympathetic Nervous System; Weight Loss

It has been suggested that sympathetic hyperactivity is found in patients with metabolic syndrome (MS) by measuring turnover rate of catecholamines and/or muscle sympathetic nerve firing rate. Increased leptin associated with MS stimulates sympathetic outflow from the hypothalamus, which may be one of causes of sympathetic hyperactivity. Insulin increased in association with insulin resistant in MS increases sodium reabsorption in the kidney leading to sodium retention. Increased intra-cranial sodium ions are known to augment sympathetic nervous system activity via stimulation of epithelial sodium channels, mineralocorticoid receptors, the renin-angiotensin-aldosterone system and endogenous digitalislike factors in the brain. This mechanism may be true in patients with essential hypertension, particularly in those who are sensitive to sodium loading.

Topics: Brain; Catecholamines; Humans; Hypertension; Insulin Resistance; Kidney; Leptin; Metabolic Syndrome; Receptors, Mineralocorticoid; Renin-Angiotensin System; Sodium; Sodium Channels; Sympathetic Nervous System

Hypertension and obesity are major components of the cardiometabolic syndrome and are both on the rise worldwide, with enormous consequences on global health and the economy. The relationship between hypertension and obesity is multifaceted; the etiology is complex and it is not well elucidated. This article, reviews the current knowledge on obesity-related hypertension. Further understanding of the underlying mechanisms of this epidemic will be important in devising future treatment avenues.

Topics: Adipocytes; Adiponectin; Animals; Humans; Hypertension; Insulin Resistance; Kidney; Leptin; Obesity; Renin-Angiotensin System; Sleep Apnea, Obstructive; Sympathetic Nervous System

Obesity and hypertension frequently coexist and both represent important risk factors for cardiovascular disease. The mechanisms implicated in the regulation of food intake have not been completely elucidated. Recent data suggests that peripheral and central neuropeptides play an important role in the maintenance of energy balance. More specifically, leptin, neuropeptide Y (NPY) and alpha-melanocyte-stimulating hormone (a-MSH) appear to be implicated in the pathogenesis of obesity and also contribute to the development of hypertension in obesity.. Analysis of the pertinent bibliography published in PubMed database.. Leptin is produced in the adipose tissue directly correlated with fat tissue mass. Leptin acts on two distinct neural populations in the hypothalamus: the first expresses the orexigenic peptides NPY and agouti-related protein (AgRP), the second pro-opiomelanocortin (POMC). The activation of POMC neurons increases the production of the anorexigenic hormone a-MSH and inhibits the release of NPY and AgRP. In addition, the hypothalamus integrates the neuroendocrine systems with the autonomic nervous system and controls the activity of the latter. Stimulation of hypothalamic nuclei elicits sympathetic responses including blood pressure elevation. Both NPY and a-MSH appears to be implicated in the hypothalamic regulation of sympathetic nervous system (SNS) activity.. Alterations in leptin, NPY and a-MSH are frequently observed in obesity and might stimulate SNS activity, contributing to the development of hypertension in obese patients. These neuropeptides might provide a pathophysiologic link between excess weight and hypertension. However, more research is needed before the pharmacologic manipulation of these complex neuroendocrine systems can be applied in the treatment of obesity and hypertension.

Topics: alpha-MSH; Appetite Regulation; Body Weight; Humans; Hypertension; Leptin; Neuropeptide Y; Obesity; Sympathetic Nervous System

The sympathetic nervous system is activated in human obesity and in the analogous experimental obesity produced by overfeeding. The causes remain uncertain and may be multiple. The consequences include hypertension, probably attributable to activation of the sympathetic outflow to the kidneys, and, more disputed, insulin resistance. The pattern of sympathetic activation in normal-weight and obesity-related hypertension differs in terms of the firing characteristics of individual sympathetic fibers (increased rate of nerve firing in normal-weight hypertensives, increased number of active fibers firing at a normal rate in obesity-hypertension) and the sympathetic outflows involved. The underlying mechanisms and the adverse consequences of the two modes of sympathetic activation may differ. Should antihypertensive drug therapy in obesity-hypertension specifically target the existing neural pathophysiology? Such an approach can be advocated on theoretical grounds. Perhaps more important is the requirement that chosen antihypertensives do not cause weight gain or insulin resistance.

Topics: Adrenergic beta-3 Receptor Agonists; Humans; Hyperinsulinism; Hypertension; Leptin; Obesity; Risk Factors; Sleep Apnea, Obstructive; Sympathetic Nervous System; Weight Loss

After an initial attempt by the WHO to define metabolic syndrome (MS) on a pathophysiologically oriented approach requiring the assessment of insulin resistance markers, the NCEP-ATPIII and more recently the IDF proposed more clinically oriented criteria to help, toward a preventive medicine goal, to identify patients who are likely to have features of the MS and be at increased risk of type 2 diabetes and cardio vascular disease. The notion of MS is built around abnormalities of the metabolism of lipids and carbon hydrates, a rise of blood pressure, and visceral obesity of abdominal localization. These parameters report only partially on mechanisms leading to the development of the MS. The physiopathology of MS is partially understood even today and likely results from the combination of environmental, genetic and epigenetic factors. Abdominal visceral obesity, a state of low-grade chronic inflammation and insulin resistance are the main processes susceptible to explain the various constituents of this syndrome.

Topics: Environment; Exercise; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Metabolic Syndrome; Models, Biological; Nutritional Status; Psoriasis

The incidence and prevalence of obesity and the metabolic syndrome have risen markedly in the past decade, representing a serious cardiovascular health hazard with significant morbidity and mortality. The etiology of the metabolic syndrome and its various pathogenic mechanisms are incompletely defined and under intense investigation. Contemporary research suggests that the adipocyte-derived hormone leptin may be an important factor linking obesity, the metabolic syndrome, and cardiovascular disorders. Although recent evidence indicates that under normal conditions leptin may be an important factor in regulating pressure and volume, during situations of chronic hyperleptinemia and leptin resistance, this hormone may function pathophysiologically for the development of hypertension and cardiac and renal diseases. Future research will determine if reduction of circulating leptin and/or blockade of its peripheral actions can confer cardiovascular and renal protection in hyperleptinemic patients with obesity and the metabolic syndrome.

Topics: Appetite Regulation; Blood Pressure; Cardiovascular Diseases; Heart; Humans; Hypertension; Insulin Resistance; Kidney; Leptin; Metabolic Syndrome; Obesity; Receptors, Leptin; Risk Factors; Sympathetic Nervous System

Currently, a high carbohydrate/low fat diet is recommended for patients with hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate plays in hypertension and the development of pathological left ventricular hypertrophy (LVH) has not been well characterized. Recent studies demonstrate that LVH can also be triggered by activation of insulin signaling pathways, altered adipokine levels, or the activity of peroxisome proliferator-activated receptors (PPARs), suggesting that metabolic alterations play a role in the pathophysiology of LVH. Hypertensive patients with high plasma insulin or metabolic syndrome have a greater occurrence of LVH, which could be due to insulin activation of the serine-threonine kinase Akt and its downstream targets in the heart, resulting in cellular hypertrophy. PPARs also activate cardiac gene expression and growth and are stimulated by fatty acids and consumption of a high fat diet. Dietary intake of fats and carbohydrate and the resultant effects of plasma insulin, adipokine, and lipid concentrations may affect cardiomyocyte size and function, particularly in the setting of chronic hypertension. This review discusses potential mechanisms by which dietary carbohydrates and fats ca affect cardiac growth, metabolism, and function, mainly in the context of pressure overload-induced LVH.

Topics: Adiponectin; Animals; Blood Glucose; Dietary Carbohydrates; Dietary Fats; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin Resistance; Leptin; Lipid Metabolism; Models, Animal

Considerable evidence has suggested that excessive weight gain is the most common cause of arterial hypertension. This association has been observed in several populations, in different regions of the world. Obesity-hypertension, a term that underscores the link between these two deleterious conditions, is an important public health challenge, because of its high frequency and concomitant risk of cardiovascular and kidney diseases. The obesity-hypertension pandemic imposes a considerable economic burden on societies, directly reflecting on healthcare system costs. Increased renal sodium reabsorption and blood volume expansion are central features in the development of obesity-hypertension. Overweight is also associated with increased sympathetic activity. Leptin, a protein expressed in and secreted by adipocytes, is the main factor linking obesity, increased sympathetic nervous system activity and hypertension. The renin-angiotensin-aldosterone system has also been causally implicated in obesity-hypertension, because angiotensinogen is expressed in and secreted by adipose tissue. Hypoadiponectinemia, high circulating levels of free fatty acids and increased vascular production of endothelin-1 (ET-1) have been reported as potential mechanisms for obesity-hypertension. Lifestyle changes are effective in obesity-hypertension control, though pharmacological treatment is frequently necessary. Despite the consistency of the mechanistic approach in explaining the causal relation between hypertension and obesity, there is yet no evidence that one class of drug is superior to the others in controlling obesity-hypertension. In this review, we present the current knowledge and research in obesity-hypertension, exploring the epidemiologic evidence of the association, its probable pathophysiological mechanisms and treatment issues.

Topics: Adolescent; Adult; Antihypertensive Agents; Child; Exercise; Female; Humans; Hypertension; Leptin; Life Style; Male; Obesity

The incidence and prevalence of obesity has risen markedly in the last decade, and this epidemic represents a serious health hazard with significant morbidity and mortality. Although hypertension is recognized as one of the most serious consequences of obesity, its pathophysiology remains incompletely understood. Contemporary research suggests that the recently discovered hormone leptin may represent a common link between these 2 pathologic conditions. Leptin is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance. By binding to receptors in the hypothalamus, it reduces food intake and promotes elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. Although the relevance of endogenous leptin needs further clarification for the control of renal sodium excretion and vascular tone, it appears to be a potential pressure and volume-regulating factor in normal situations. However, in conditions of chronic hyperleptinemia, such as obesity, leptin may function pathophysiologically for the development of hypertension as well as cardiac and renal disease. Thus, in addition to weight control, reduction of circulating leptin may confer cardiovascular and renal protective effects in patients with obesity-hypertension.

Topics: Blood Pressure; Heart Diseases; Humans; Hypertension; Kidney Diseases; Leptin; Obesity; Sympathetic Nervous System

A cluster of risk factors associated with obesity defines the metabolic syndrome and identifies cardiometabolic risk. Accumulation of fat in the visceral depot is a more reliable predictor of cardiovascular disease than is total body mass or body mass index. The recent discovery of the endocannabinoid-CB1 receptor system and its impact on the regulation of energy metabolism represents a significant advance that will help target visceral fat and its metabolic implications. As a highly active endocrine organ, visceral fat secretes many bioactive molecules, known as adipokines. Dysregulation of these adipokines contributes to the pathogenesis of the obesity-associated metabolic syndrome, resulting in insulin resistance, type 2 diabetes, hypertension, hyperlipidemia, and vascular disease. Even modest weight reduction leads to reduced cardiometabolic risk by affecting the individual components comprising the metabolic syndrome.

Topics: Adiponectin; Anti-Obesity Agents; Blood Coagulation; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diet; Dyslipidemias; Exercise; Fatty Acids; Humans; Hypertension; Inflammation Mediators; Insulin Resistance; Intra-Abdominal Fat; Leptin; Life Style; Metabolic Syndrome; Obesity; Practice Guidelines as Topic; Risk Factors; Weight Loss

Unique genetic traits appear to play a role in the increased rates of hypertension (HTN), glucose dysregulation/diabetes (T2DM), and obesity in persons of African descent. Indeed, with increasing rates of westernization/urbanization and concomitant increases in obesity and T2DM, a similar predisposition to the cardiometabolic syndrome and cardiovascular disease (CVD) can be seen in Africans compared with persons of African descent, with CVD reaching epidemic proportions in many areas of Africa. In addition, the complex relationships of metabolic abnormalities that are unique to individuals of African descent have also been demonstrated in Africans. These include: (1) a dissociation of HTN to insulin resistance; (2) relative favorable lipid profile in the setting of increasing rates of CVD; (3) low levels of visceral adiposity in the setting of obesity and insulin resistance; and (4) a dissociation of insulin sensitivity and adiponectin when compared with Caucasians. Although not well understood, these unique relationships suggest that conventional parameters for CVD do not apply to Africans of persons of African descent.

Topics: Adiponectin; Africa; Diabetes Mellitus, Type 2; Dyslipidemias; Genetic Predisposition to Disease; Humans; Hypertension; Insulin Resistance; Leptin; Life Style; Metabolic Syndrome; Obesity; Risk Factors

Leptin is a recently isolated circulating peptide hormone that is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake, elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. While the relevance of endogenous leptin needs further clarification, it appears to be a potential pressure- and volume-regulating factor, and may function pathophysiologically as a common link to obesity and hypertension.

Topics: Animals; Hemodynamics; Humans; Hypertension; Kidney; Leptin; Obesity; Receptors, Cell Surface; Receptors, Leptin; Sympathetic Nervous System

Topics: Aldosterone; Biological Transport; Calmodulin-Binding Proteins; Catecholamines; Hypertension; Insulin; Intracellular Signaling Peptides and Proteins; Ions; Kidney; Leptin; Mutation; Potassium Channels; Protein Subunits; Sodium; Sodium-Potassium-Exchanging ATPase

Topics: Adipose Tissue; Adult; Body Mass Index; Exercise Therapy; Humans; Hypertension; Kidney Diseases; Leptin; Obesity; Racial Groups; Risk Factors; Treatment Outcome

Leptin is a 16-kDa protein secreted by white adipose tissue that is primarily involved in the regulation of food intake and energy expenditure. Plasma leptin concentration is proportional to the amount of adipose tissue and is markedly increased in obese individuals. Recent studies suggest that leptin is involved in cardiovascular complications of obesity, including arterial hypertension. Acutely administered leptin has no effect on blood pressure, probably because it concomitantly stimulates the sympathetic nervous system and counteracting depressor mechanisms such as natriuresis and nitric oxide (NO)-dependent vasorelaxation. By contrast, chronic hyperleptinemia increases blood pressure because these acute depressor effects are impaired and/or additional sympathetic nervous system-independent pressor effects appear, such as oxidative stress, NO deficiency, enhanced renal Na reabsorption and overproduction of endothelin. Although the cause-effect relationship between leptin and high blood pressure in humans has not been demonstrated directly, many clinical studies have shown elevated plasma leptin in patients with essential hypertension and a significant positive correlation between leptin and blood pressure independent of body adiposity both in normotensive and in hypertensive individuals. In addition, leptin may contribute to end-organ damage in hypertensive individuals such as left ventricular hypertrophy, retinopathy and nephropathy, independent of regulating blood pressure. Here, current knowledge about the role of leptin in the regulation of blood pressure and in the pathogenesis of arterial hypertension is presented.

Topics: Animals; Blood Pressure; Forecasting; Humans; Hypertension; Leptin; Models, Biological; Natriuresis; Nitric Oxide; Sodium-Potassium-Exchanging ATPase

For better understanding the role of each element involved in the physiopathology of obesity and insulin resistance, researchers can use experimental models, which may in controlled manner evaluate the participation of each element on the obesity and insulin resistance and provide information for better understanding the physiopathology and treatment of obesity and insulin resistance. Experimental obesity and insulin resistance can be due to a deficient response to leptin, secondary to hypoleptinemia and/or mutations on leptin receptor, by modifications on insulin receptor, deletion or diminished insulin signal transduction, enhancement of the effects of orexigen peptides and/or diminution of anorexigen peptides actions on hypothalamus, as well as secondary to arterial hypertension, as in the spontaneously hypertension. Obesity and insulin resistance can also be induced by glucocorticoid excess, frutose enriched and cafeteria diet and due to hypothalamus lesions induced by neonatal administration of monossodium glutamate.

Topics: Adipose Tissue; Animals; Diet; Disease Models, Animal; Hypertension; Insulin Resistance; Leptin; Models, Genetic; Models, Immunological; Obesity

Endothelial dysfunction is associated with several vascular conditions as atherosclerosis, hypertension, hyperlipidemia and diabetes mellitus. In all these conditions insulin resistance (IR) is present. Cytokines are low molecular weight proteins with several endocrine and metabolic functions that participate of inflammation and immune response. Several of these cytokines are independent risk factors for cerebrovascular and coronary artery disease. The major sources of cytokines (adipokines) are the visceral and subcutaneous adipose tissues. Thus, increased adipose tissue mass is associated with alteration in adipokine production as over expression of tumor necrosis factor alpha, interleukin 6, plasminogen activator inhibitor 1, and under expression of adiponectin in adipocite tissue. The pro-inflammatory status associated with these changes provides a potential link between IR and endothelial dysfunction, the early stage in the atherosclerotic process, in obese individuals, and type 2 diabetic patients. Reduction of adipose tissue mass through weight reduction in association with exercise reduces TNF-alpha, IL-6, and PAI-1, increases adiponectin, and is associated with improved insulin sensitivity and endothelial function. This review will focus on the evidence for regulation of endothelial function by insulin and the adypokines such as adyponectin, leptin, resistin, IL-6 and TNF-alpha. Interaction between insulin signaling and adypokines will be discussed, as well as the concept that aberrant adypokine secretion in IR and/or obesity impairs endothelial function and contributes further to reduce insulin sensitivity.

Topics: Adiponectin; Cardiovascular Diseases; Cytokines; Endothelium, Vascular; Fatty Acids; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin

Topics: Animals; Arteriosclerosis; Energy Metabolism; Humans; Hypertension; Leptin; Obesity; Receptors, Cell Surface; Receptors, Leptin; Risk Factors; Sympathetic Nervous System; Ventromedial Hypothalamic Nucleus

Topics: Amino Acid Sequence; Animals; Disease Models, Animal; Energy Metabolism; Humans; Hypertension; Leptin; Mice; Mice, Obese; Molecular Sequence Data; Mutation; Obesity; Receptors, Cell Surface; Receptors, Leptin; Sympathetic Nervous System

Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Humans; Hypertension; Insulin Resistance; Leptin; Life Style; Metabolic Syndrome; Obesity; Sympathetic Nervous System

Topics: Animals; Carbon Monoxide; Disease Models, Animal; Hypertension; Insulin Resistance; Leptin; Natriuresis; Nitric Oxide; Nitric Oxide Synthase; Obesity; Oxidative Stress; Rats; Rats, Zucker; Receptors, Cell Surface; Receptors, Dopamine; Receptors, Leptin; Renin-Angiotensin System

Stroke is an important cause of morbidity and mortality, and is an economic burden. Diabetes and obesity are two important modifiable risk factors for stroke. Patients with diabetes have a higher incidence of stroke and a poorer prognosis after stroke. Risk-factor modification is the most important aspect of prevention of stroke in diabetes and obesity. This includes lifestyle modifications and different therapeutic modalities to control conditions, such as diabetes, hypertension, dyslipidemia and arrhythmia. Recent landmark studies have shown the beneficial effects of statins in diabetic patients even with close to normal or normal low-density lipoprotein cholesterol. Obesity, which is a risk factor for diabetes, hypertension and hyperlipidemia has been shown to be an independent risk factor for stroke. Increased leptin, dysregulation of adipocyte proteins, increased insulin resistance and C-reactive protein may be factors involved in the increased incidence of cardiovascular morbidity and mortality directly related to obesity. Visceral fat is a much bigger health risk than subcutaneous fat. Lifestyle interventions and pharmacotherapeutic agents have been used to manage obesity. In morbidly obese patients, surgical intervention seems to be the best method of treatment with a long-lasting favorable metabolic outcome. In the 21st Century, with the advanced medical knowledge and the therapeutic modalities available, it should be possible to reduce the incidence of stroke associated with diabetes and obesity.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Atrial Fibrillation; Blood Glucose; Cardiovascular Agents; Carotid Stenosis; Diabetes Mellitus; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Dyslipidemias; Humans; Hypertension; Insulin Resistance; Ischemic Attack, Transient; Leptin; Life Style; Lipoproteins; Obesity; Plasminogen Activator Inhibitor 1; Risk Factors; Smoking; Stroke

1. The current worldwide epidemic of obesity and its major complications, namely type 2 diabetes and hypertension, is well documented. The present mini-review develops the thesis that 'thrifty' metabolic traits, evolved in the setting of intermittent famine, contribute to the obesity pandemic. 2. These thrifty traits, namely a decreased capacity for dietary thermogenesis and an increased resistance to insulin-mediated glucose uptake in skeletal muscle, would prolong survival during famine but predispose to obesity and diabetes in the face of abundance. The regulation of dietary thermogenesis by the sympathetic nervous system also explains the well-established association between obesity and high blood pressure. 3. These observations provide a deep-seated rationale for the efficacy of lifestyle interventions in the treatment of obesity and its complications and may also provide a predicate for the development of new therapeutic strategies aimed at neutralizing the impact of these thrifty traits. Such strategies may entail, for example, therapeutic agents that enhance metabolic rate during low-energy diets, thereby reversing the physiological impediment imposed by suppression of the sympathetic nervous system.

Topics: Diabetes Mellitus; Diet; Eating; Energy Metabolism; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Models, Biological; Obesity; Overnutrition; Quantitative Trait, Heritable; Sympathetic Nervous System; Thermogenesis

Leptin, the product the ob gene, is secreted by adipocytes to regulate energy homeostasis. This hormone may have an important influence on blood pressure, leading to hypertension. Leptin, acting in the hypothalamic melanocortin system, can activate or inactivate neuropeptides and produce hypertension, mainly by renal, adrenal, and muscular sympathoactivation. The role of leptin in regulating cardiovascular function in obesity is presented based on contemporary literature. Both intracellular signaling pathways activated by leptin and the role of leptin receptors are also discussed. The roles of endogens, neuropeptides in food intake, and energy expenditure are also presented.

Topics: Adipose Tissue; Energy Metabolism; Humans; Hypertension; Hypothalamus; Leptin; Obesity; Receptors, Cell Surface; Receptors, Leptin; Signal Transduction; Sympathetic Nervous System

To review the potential role of leptin, hyperleptinaemia and leptin resistance in the cardiovascular and endocrine complications of metabolic syndrome.. Review of literature listed in Medline.. Hyperleptinaemia is common in obesity and reflects increased adiposity and leptin resistance. Nevertheless, leptin resistance may not be complete as several actions of leptin, such as cardiovascular sympatho-activation, might be preserved in obese subjects known to be resistant to the metabolic effects of leptin (i.e. selective leptin resistance). Notably, the renal and sympathetic actions of leptin may play an important role in the pathogenesis of hypertension related to obesity and metabolic syndrome. Furthermore, the lipotoxic effect of leptin resistance may cause insulin resistance and beta cell dysfunction, increasing the risk of type 2 diabetes. Leptin has also been shown to possess proliferative, pro-inflammatory, pro-thrombotic, and pro-oxidative actions.. Hyperleptinaemia and leptin resistance may contribute to hypertension, impaired glucose metabolism, and pro-atherogenic state in obesity and metabolic syndrome.

Topics: Animals; Atherosclerosis; Blood Pressure; Diabetes Mellitus, Type 2; Drug Resistance; Humans; Hypertension; Insulin Resistance; Leptin; Metabolic Syndrome; Obesity

Leptin, a peptide discovered more than 10 years ago, decreases food intake and increases sympathetic nerve activity to both thermogenic and non-thermogenic tissue. Leptin was initially believed to be an anti-obesity hormone, owing to its metabolic effects. However, obese individuals, for unknown reasons, become resistant to the satiety and weight-reducing effect of the hormone, but preserve leptin-mediated sympathetic activation to non-thermogenic tissue such as kidney, heart, and adrenal glands. Leptin has been shown to influence nitric oxide production and natriuresis, and along with chronic sympathetic activation, especially to the kidney, it may lead to sodium retention, systemic vasoconstriction, and blood pressure elevation. Consequently, leptin is currently considered to play an important role in the development of hypertension in obesity.

Topics: Abdominal Fat; Animals; Antihypertensive Agents; Appetite Regulation; Blood Pressure; Body Weight; Energy Metabolism; Humans; Hypertension; Kidney; Leptin; Nitric Oxide; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Time Factors

Obesity is strongly associated with hypertension and cardiovascular disease. Several central and peripheral abnormalities that can explain the development or maintenance of high arterial pressure in obesity have been identified. These include activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system. Obesity is also associated with endothelial dysfunction and renal functional abnormalities that may play a role in the development of hypertension. The continuing discovery of mechanisms regulating appetite and metabolism is likely to lead to new therapies for obesity-induced hypertension. Better understanding of leptin signaling in the hypothalamus and the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance. Other hunger and satiety signals such as ghrelin and peptide YY are potentially attractive therapeutic strategies for treatment of obesity and its complications. These recent discoveries should lead to novel strategies for treatment of obesity and hypertension.

Topics: Adiponectin; Aldosterone; Animals; Appetite; Endothelium, Vascular; Energy Metabolism; Ghrelin; Humans; Hyperinsulinism; Hypertension; Intercellular Signaling Peptides and Proteins; Kidney; Leptin; Mice; Mice, Mutant Strains; Mineralocorticoid Receptor Antagonists; Obesity; Peptide Hormones; Peptide YY; Receptors, Cell Surface; Receptors, Leptin; Renin-Angiotensin System; Repressor Proteins; Satiation; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Sympathetic Nervous System; Transcription Factors

The metabolic syndrome, an emerging public health problem, represents a constellation of cardiovascular risk factors. It has been suggested that the presence of obstructive sleep apnea (OSA) may increase the risk of developing some of the features of the metabolic syndrome, including hypertension, insulin resistance, and type 2 diabetes. In this article, we discuss the parallels between the metabolic syndrome and obstructive sleep apnea and describe possible OSA-related factors that may contribute to the metabolic syndrome, specifically the roles of obesity, hypertension, dyslipidemia, sex hormones, inflammation, vascular dysfunction, leptin, insulin resistance, and sleep deprivation.

Topics: Female; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Polycystic Ovary Syndrome; Risk Factors; Sleep Apnea, Obstructive

Fatty tissue synthesizes and secretes a wide range of products that may be directly involved in the pathogenesis of the complications associated with obesity. These so-called adipokines may trigger or sustain a chronic inflammatory process. By manipulating the secretory function of fat cells, it might in future be possible to prevent the development of the metabolic and cardiovascular complications of obesity. Current data already suggest that weight reduction and certain substances with an anti-inflammatory action reduce the risk for the metabolic and cardiovascular complications of obesity. To date, however, the evidence available is only indirect, and is insufficient to definitively establish causal relationships between certain secretory products of adipocytes and the comorbidities of adiposity. Further clinical studies are needed.

Topics: Adipocytes; Adiponectin; Adipose Tissue; Animals; Coronary Disease; Diabetes Mellitus, Type 2; Humans; Hypertension; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Metabolic Syndrome; Obesity; Plasminogen Inactivators; Risk Factors; Thromboembolism; Weight Loss

Topics: Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Disease Progression; Endothelial Cells; Glucose Intolerance; Humans; Hypertension; Insulin Resistance; Leptin; Life Style; Obesity

Leptin and ghrelin are novel peptide hormones which are counter-regulatory in the central control of appetite. More recently, it has become clear that these hormones have a range of effects on the cardiovascular system. Leptin increases sympathetic activity, producing a pressor effect when acting on the central nervous system. However, leptin produces vasodilation by an endothelium-dependent mechanism peripherally. Ghrelin decreases sympathetic activity and has a depressor effect when acting on the central nervous system. Peripherally, ghrelin produces vasodilation by an endothelium-independent mechanism. Ghrelin improves left ventricular function and cardiac cachexia in heart failure. Leptin may contribute to cardiac cachexia, and to obesity-related cardiomyopathy by a variety of mechanisms. Leptin has pro-inflammatory, proliferative and calcification promoting effects in the vasculature. Ghrelin has recently been shown to be anti-inflammatory in the vasculature. Leptin may also produce a pro-thrombotic state through stimulation of platelet aggregation and inhibition of coagulation and fibrinolysis. The evidence for and against these effects as well as their pathophysiological significance in obesity hypertension, heart failure, atherosclerosis and thrombosis are discussed.

Topics: Animals; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Ghrelin; Heart Failure; Humans; Hypertension; Leptin; Obesity; Peptide Hormones; Thrombosis

Earlier ideas that sympathetic nervous system activity is low in human obesity, contributing to weight gain through absence of sympathetically mediated thermogenesis, can now be discounted. The application of sympathetic nerve recording techniques and isotope dilution methodology quantifying neurotransmitter release from sympathetic nerves has established that the sympathetic outflows to the kidneys and skeletal muscle vasculature are activated in obese humans. The cause remains unclear. The adipocyte hormone, leptin, stimulates the sympathetic nervous system in rodents, but whether this applies in humans is uncertain. Cross-sectional studies suggest a quantitative link exists between regional sympathetic nervous tone (most notably in the kidneys) and rates of leptin release, but definitive studies documenting that leptin administration activates the human sympathetic nervous system have not been done. What might be the clinical implications of these new findings? The demonstration that the suppressed sympathetic tone characterizing many experimental models of obesity does not exist in human obesity weakens the case for the use of beta3-adrenergic agonists as thermogenic agents to facilitate weight loss. Although the neurogenic character of obesity-related hypertension is now established, whether antiadrenergic antihypertensive drugs are the preferred agents for blood pressure reduction has not been adequately tested. Multiple site central venous sampling, disclosing release of leptin into the internal jugular veins, led to the demonstration that the leptin gene is also expressed in the brain, in addition to adipocytes. Brain resistance to leptin has been inferred in human obesity, given that overweight is accompanied by high plasma leptin levels. The fact that the genes for leptin and its receptors are normally expressed in the brain in human obesity, and that release of leptin from the brain is actually increased, argues against this. Brain leptin release has the potential to override the peripheral, adipocyte leptin system.

Topics: Adrenergic beta-Antagonists; Animals; Brain; Enzyme Inhibitors; Humans; Hypertension; Leptin; Lipase; Norepinephrine; Obesity; Selective Serotonin Reuptake Inhibitors; Sympathetic Nervous System

Obesity in humans causes hypertension, myocardial hypertrophy and coronary atherosclerosis, and increased cardiovascular morbidity and mortality that is thought to be related to sympathetic overactivity. Leptin is an adipocyte-derived hormone that acts in the hypothalamus to regulate appetite, energy expenditure and sympathetic nervous system outflow. One of the major mechanisms leading to the development of obesity-induced hypertension appears to be leptin-mediated sympatho-activation. Leptin adversely shifts the renal pressure-natriuresis curve, leading to relative sodium retention. Although obesity is generally associated with resistance to the anorexic and weight-reducing actions of leptin, our work has shown preservation of its sympatho-excitatory and pressor actions. This selective leptin resistance of obesity, coupled with hyperleptinaemia, may play a critical role in the cardiovascular complications of obesity. Increased information about leptin and its mechanisms of actions should help the development of safe and effective pharmacological treatments of obesity and obesity-related hypertension.

Topics: alpha-MSH; Animals; Blood Pressure; Corticotropin-Releasing Hormone; Drug Resistance; Humans; Hypertension; Leptin; Neuropeptide Y; Obesity; Receptors, Cell Surface; Receptors, Leptin; Sympathetic Nervous System

Leptin is a recently isolated circulating peptide hormone that is primarily synthesized and secreted by adipocytes. One of the major functions of this hormone is the control of energy balance by binding to receptors in the hypothalamus, leading to reduction in food intake, elevation in temperature and energy expenditure. In addition, increasing evidence suggests that leptin, through both direct and indirect actions, may play an important role in cardiovascular and renal functions. While the relevance of endogenous leptin needs further clarification, it appears to be a potential pressure- and volume-regulating factor, and may function pathophysiologically as a common link to obesity and hypertension.

Topics: Adipocytes; Animals; Binding, Competitive; Humans; Hypertension; Leptin; Obesity; Receptors, Cell Surface; Receptors, Leptin

The insulin resistance (metabolic) syndrome (IRS), also known as syndrome X, is characterized by a clustering of factors associated with cardiovascular risk (obesity, impaired glucose metabolism, hypertension, and dyslipidemia). As reported from the third National Health and Nutrition Examination survey, the IRS is present in approximately 24% of adults in the United States and is strongly associated with coronary heart disease, stroke, type 2 diabetes, and all-cause mortality. Of equal importance, it is now clear that the origins of the IRS extend back into childhood (the IRS is found in approximately 4-10% of children and adolescents) and that the high prevalence of adult IRS is strongly linked to the development of cardiovascular risk during childhood and tracking of the components of the IRS into adulthood. The goal of this review is to present a summary of the currently available information on the IRS in the pre-adult age group with reference to adult studies only when necessary for clarification. The review will specifically summarize insulin resistance in childhood; the important influence of obesity and, in particular, visceral fat, on insulin resistance and the IRS; differences between ethnic groups; relations to adipocytokines, inflammatory factors and oxidative stress; relations of hypertension and lipids to insulin resistance; familial factors; endocrine complications; and potential therapeutic effects from diet and physical activity. Despite the lesser amount of basic and clinical information on childhood IRS in comparison to information available from adult studies, there can now be little doubt that the adverse associations among risk factors comprising the IRS begin in childhood. The challenge is to identify etiologic relations and develop intervention strategies designed to reduce the increasing prevalence of type 2 diabetes and cardiovascular disease.

Topics: Adolescent; C-Reactive Protein; Child; Humans; Hypertension; Insulin Resistance; Intra-Abdominal Fat; Leptin; Lipoproteins, VLDL; Metabolic Syndrome; Obesity; Oxidative Stress; Risk Factors

Obesity is a common problem in much of the western world today in that is linked directly with several disease processes, notably, hypertension. It is becoming clear that the adipocyte is not merely an inert organ for storage of energy but that it also secretes a host of factors that interact with each other and may result in elevated blood pressure. Of particular importance is the putative role of leptin in the causation of hypertension via an activation of the sympathetic nervous system and a direct effect on the kidneys, resulting in increased sodium reabsorption leading to hypertension. Obesity per se may have structural effects on the kidneys that may perpetuate hypertension, leading to an increased incidence of end-stage renal disease that results in further hypertension. Adipose tissue may elaborate angiotensin from its own local renin-angiotensin system. The distribution of body fat is considered important in the genesis of the obesity-hypertension syndrome, with a predominantly central distribution being particularly ominous. Weight loss is the cornerstone in the management of the obesity-hypertension syndrome. It may be achieved with diet, exercise, medications, and a combination of these measures. Anti-obesity medications that are currently undergoing clinical trials may play a promising role in the management of obesity and may also result in lowering of blood pressure. Antihypertensives are considered important components in the holistic approach to the management of this complex problem.

Topics: Adipose Tissue; Aldosterone; Animals; Body Mass Index; Humans; Hypertension; Inflammation; Insulin Resistance; Kidney; Leptin; Metabolic Syndrome; Neuropeptides; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Thrombosis

Arterial hypertension is one of the major risk factors in cardiovascular and renal disease. Advances in the study of pathophysiologic mechanisms and the relationship between several regulatory systems provide the basis for development of more selective therapeutic strategies. The increasing understanding of the role played by ETs, natriuretic peptides, AM, and leptin opens new frontiers in the care of hypertension and its complications, coronary artery disease and heart failure and other forms of cardiovascular disease.

Topics: Adrenomedullin; Animals; Antihypertensive Agents; Cardiovascular System; Endothelins; Humans; Hypertension; Leptin; Natriuretic Peptides; Peptides

It is now recognized that the white adipose tIssue (WAT) produces a variety of bioactive peptIdes, collectively termed "adipokines". Alteration of WAT mass in obesity or lipoatrophy, affects the production of most adipose secreted factors. Since both conditions are associated with multiple metabolic disorders and increased risk of cardiovascular diseases, the Idea has emerged that WAT could be instrumental in these complications, by virtue of its secreted factors. Several adipokines are increased in the obese state and have been implicated in hypertension (angiotensinogen), impaired fibrinolysis (PAI-1) and insulin resistance (ASP, TNFalpha, IL-6, resistin). Conversely, leptin and adiponectin both exert an insulin-sensitizing effect, at least in part, by favoring tIssue fatty-acId oxIdation through activation of AMP-activated kinase. In obesity, insulin resistance has been linked to leptin resistance and decreased plasma adiponectin. In lipoatrophic mice, where leptin and adiponectin circulating levels are low, administration of the two adipokines synergistically reverses insulin resistance. Leptin and adiponectin also have distinct properties: leptin, as a long-term integrative signal of energy store and adiponectin, as a potent anti-atherogenic agent. The thiazolIdinedione anti-diabetic drugs increase endogenous adiponectin production in rodents and humans, supporting the Idea that the development of new drugs targeting adipokines might represent a promising therapeutic approach to protect obese patients from insulin resistance and atherosclerosis.

Topics: Adiponectin; Adipose Tissue; Animals; Fibrinolysis; Hormones, Ectopic; Humans; Hypertension; Insulin; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Plasminogen Activator Inhibitor 1; Proteins; Resistin; Tumor Necrosis Factor-alpha

Obesity is a risk factor for cardiovascular diseases, in particular for hypertension. Serum leptin levels and sympathetic nerve activity are both increased in obesity. Leptin has been demonstrated to increase sympathetic nerve activity. Thus, leptin-dependent sympathoactivation might contribute to obesity-related hypertension. However, leptin resistance occurs in obesity. One possibility is that leptin resistance is selective to the metabolic effects of leptin, sparing its sympathoexcitatory actions. In this article, we review experimental evidence supporting the novel concept of selective leptin resistance. We also discuss the sympathetic actions of leptin that are relevant to blood pressure modulation and potential mechanisms of leptin resistance. Disruption of leptin intracellular signaling pathways and resistance of specific leptin-responsive neural networks provide theoretic models of selective leptin resistance. However, most information about leptin-sympathetic actions and leptin-resistance mechanisms derive from in vitro and animal studies. Future research in humans is widely awaited.

Topics: Blood Pressure; Drug Resistance; Humans; Hypertension; Leptin; Nerve Net; Neural Pathways; Obesity; United States

Topics: Antihypertensive Agents; Body Mass Index; Catecholamines; Diet, Reducing; Exercise Therapy; Humans; Hypertension; Insulin Resistance; Leptin; Life Style; Obesity; Reference Standards; Risk Factors

Topics: Adipocytes; Animals; Arteriosclerosis; Cell Differentiation; Humans; Hypertension; Insulin Resistance; Leptin; Ligands; Lipid Metabolism; Macrophage Activation; Metabolic Syndrome; Neovascularization, Pathologic; Receptors, Cytoplasmic and Nuclear; Thiazolidinediones; Transcription Factors; Vascular Endothelial Growth Factor A

Topics: Animals; Diet, Reducing; Energy Metabolism; Humans; Hypertension; Leptin; Receptors, Cell Surface; Receptors, Leptin; Sympathetic Nervous System

The renin-angiotensin system (RAS) and the endothelin system have been implicated in the pathogenesis of human cardiovascular and renal diseases, and inhibition of the RAS markedly improves morbidity and survival. Obesity in humans is associated with an increased risk for the development of hypertension, atherosclerosis and focal-segmental glomerulosclerosis, however the exact mechanisms underlying these pathologies in obese individuals are not known. This article discusses the clinical importance of obesity and the current evidence for local activation of the renin-angiotensin system and its interactions with the endothelin system in obesity and the cardiovascular pathologies associated with it.

Topics: Adipocytes; Adiponectin; Angiotensin II; Animals; Endothelin-1; Endothelium, Vascular; Hormones, Ectopic; Humans; Hypertension; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Kidney; Leptin; Mice; Nerve Growth Factor; Obesity; Proteins; Rats; Renin-Angiotensin System; Resistin

Obesity, which has reached epidemic prevalence, is now recognized as an independent risk factor for increasing blood pressure. The complex mechanisms of obesity-related hypertension are unclear, but several studies have provided evidence of a hypertensive shift in pressure natriuresis. Excess sympathetic outflow to the kidneys and changes in renal structure and function may both affect the renal pressure relationship. Other factors that may contribute to altered natriuresis include hyperinsulinemia, hyperleptinemia and activation of the renin-angiotensin system. Disruption of the renal alpha2 adrenoceptors or leptin receptor implicated in natriuresis control may also be an additive risk for the increase in tubular reabsorption in obesity hypertension.. Recent advances have highlighted the importance of two adipocyte-derived hormones - leptin and angiotensinogen - in obesity hypertension. Leptin has direct central effects that increase sympathetic outflow to the kidney and the new concept of selective leptin resistance, suggests the maintenance of leptin-induced sympathetic activation in obesity, despite resistance to leptin metabolic effects. On the other hand, a recent study showed that angiotensinogen produced in the adipocyte is also relevant to blood pressure control.. The article reviews the factors implicated in the disruption of blood pressure control in obesity. Further investigation on the time course of the disease would reveal the relative importance of each of the factors that influence the risk of hypertension in obese individuals.

Topics: Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Obesity; Renin-Angiotensin System; Risk Factors; Sympathetic Nervous System

Several previous studies confirmed that obesity is a major risk factor for the development of cardiovascular diseases, including hypertension. A large number of clinical studies considered the role of the sympathetic nervous system in linking obesity with hypertension, and there is substantial evidence that human obesity is characterized by defects in sympathetic cardiovascular control. The association of obesity with hypertension has been well documented in most racial, ethnic, and socioeconomic groups. Ethnicity may be an important factor to consider since sympathetic nervous system activity, and the propensity for obesity and hypertension, all differ substantially among different populations. Obesity is actually accompanied by increased sympathetic nerve discharge to skeletal muscles, a main site for energy expenditure. Adiposity-related sympathetic overactivity is a compensatory mechanism to burn fat and decrease weight gain, but at the cost of increased sympathetic discharge to the peripheral vasculature, which could predispose to hypertension. Thus, sympathetic nervous system activity is important in the development and maintenance of obesity-related hypertension in different racial and ethnic populations, including white and black Americans.

Topics: Black People; Comorbidity; Energy Metabolism; Humans; Hypertension; Leptin; Muscle, Skeletal; Obesity; Sympathetic Nervous System; White People

The obesity epidemic is driving metabolic (insulin resistance) syndrome-related health problems including an approximately threefold increased coronary heart disease risk. Sympathetic hyperfunction may participate in the pathogenesis and complications of the metabolic syndrome including higher blood pressure, a more active renin-angiotensin system, insulin resistance, faster heart rates, and excess cardiovascular disease including sudden death. Possible factors augmenting sympathetic activation in the metabolic syndrome include alterations of insulin, leptin, nonesterified fatty acids (NEFAs), cytokines, tri-iodothyronine, eicosanoids, sleep apnea, nitric oxide, endorphins, and neuropeptide Y. Of note, high plasma NEFAs are a risk factor for hypertension and sudden death. In short-term human studies, NEFAs can raise blood pressure, heart rate, and a(1)-adrenoceptor vasoreactivity, while reducing baroreflex sensitivity, endothelium-dependent vasodilatation, and vascular compliance. Efforts to further identify the mechanisms and consequences of sympathetic dysfunction in the metabolic syndrome may provide insights for therapeutic advances to ameliorate the excess cardiovascular risk and adverse outcomes.

Topics: Cardiovascular Diseases; Fatty Acids, Nonesterified; Humans; Hypertension; Insulin Resistance; Leptin; Metabolic Syndrome; Muscle, Skeletal; Obesity; Risk Factors; Sleep Apnea Syndromes; Sympathetic Nervous System

Both type 2 diabetes and hypertension are multifactorial diseases. Several lines of evidence suggested that common genetic factors contribute to both conditions. Genes responsible for obesity and insulin resistance are candidates for common genetic factors. Among candidate genes are genes encoding glycogen synthase, beta 3-adrenergic receptor, glycogen-associated regulatory subunit of protein phosphatase-1, peroxisome proliferator--activated receptor-gamma (PPAR gamma), leptin and adiponectin. In addition, recent genome scans mapped loci linked to type 2 diabetes, hypertension and/or metabolic syndrome. Identification of genes responsible for both type 2 diabetes and hypertension will increase our understanding of molecular mechanisms of these conditions and facilitate the development of effective methods for prevention and intervention of diabetes and hypertension as well as metabolic syndrome.

Topics: Adiponectin; Animals; Diabetes Complications; Diabetes Mellitus; Glycogen Synthase; Humans; Hypertension; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Proteins; Receptors, Adrenergic, beta-3; Receptors, Cytoplasmic and Nuclear; Transcription Factors

Diabetes mellitus and hypertension are often associated with each other, and both are risk factors for cardiovascular diseases. Insulin resistance has been noted as an etiology for diabetes, hypertension and atherosclerosis. Insulin resistance often accompanied hyperinsulinemia and it is thought to elevate blood pressure through stimulation of the sympathetic nervous system and renin-angiotensin system, promotion of sodium retention in the renal tubules, and proliferation of vascular smooth muscle cells via insulin-like growth factor. Also high blood glucose may impair vascular endothelial cells and produce oxidant stress. To prevent the occurrence of hypertension in diabetes patients, improving insulin resistance have to be considered, and primary care such as reducing body weight, salt and alcohol restriction, exercise and non-smoking are important.

Topics: Arteriosclerosis; Diabetes Mellitus, Type 2; Endothelium, Vascular; Humans; Hyperinsulinism; Hypertension; Insulin Resistance; Leptin; Life Style; Oxidative Stress; Primary Prevention; Renin-Angiotensin System; Sympathetic Nervous System

Excess weight gain is a major cause of increased blood pressure in most patients with essential hypertension, and also greatly increases the risk for renal disease. Obesity raises blood pressure by increasing renal tubular reabsorption, impairing pressure natriuresis, causing volume expansion due to activation of the sympathetic nervous system and renin-angiotensin system, and by physical compression of the kidneys, especially when visceral obesity is present. The mechanisms of sympathetic nervous system activation in obesity may be due, in part, to hyperleptinemia that stimulates the hypothalamic pro-opiomelanocortin pathway. With prolonged obesity, there may be a gradual loss of nephron function that worsens with time and exacerbates hypertension. Weight reduction is an essential first step in the management of obesity hypertension and renal disease. Special considerations for the obese patient, in addition to adequately controlling the blood pressure, include correction of the metabolic abnormalities and protection of the kidneys from further injury.

Topics: Animals; Humans; Hypertension; Kidney Diseases; Leptin; Obesity; Renin-Angiotensin System; Sympathetic Nervous System

Obstructive sleep apnea is a common disorder that is often unrecognized and underappreciated. Emerging evidence suggests that there is a causal link between obstructive sleep apnea and hypertension. This relationship appears to be independent of other comorbidities that have been previously linked to hypertension, such as obesity. The majority of studies support the contention that alleviation of sleep disordered breathing has a clinically significant beneficial impact on decreasing both nighttime and daytime blood pressure. A pathophysiologic basis for patients with sleep apnea having an increased risk for hypertension is not fully elucidated. However, there is consistent evidence that autonomic mechanisms are implicated. Sympathetic activation along with humoral responses to repetitive episodes of hypoxemia and apnea over the longer term may cause vasoconstriction, endothelial dysfunction, and possibly hypertension. Patients with sleep apnea are often obese and may be predisposed to weight gain. Hence, obesity may further contribute to hypertension in this patient population.

Topics: Blood Pressure; Endothelin-1; Female; Humans; Hypertension; Leptin; Male; Obesity; Positive-Pressure Respiration; Risk Factors; Sleep Apnea, Obstructive; Sympathetic Nervous System

This article has discussed some of the mechanisms involved in the causal relation between obesity and hypertension. Obesity causes a constellation of maladaptive disorders that individually and synergistically contribute to hypertension, among other cardiovascular morbidities. Well-designed population-based studies are needed to assess the individual contribution of each of these disorders to the development of hypertension. In addition, because the control of obesity may eliminate 48% of the hypertension in whites and 28% in blacks, this article has offered an up-to-date on the management of this problem. It is hoped that this article will help scientists formulate a thorough understanding of obesity hypertension and form the basis for more research in this field, which has a huge impact on human life.

Topics: Adipose Tissue; Aldosterone; Body Mass Index; Cardiovascular System; Genetic Predisposition to Disease; Hormones; Humans; Hypertension; Inflammation; Kidney; Leptin; Neuropeptides; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Thrombosis

Large longitudinal studies showed the epidemiological link between obesity and hypertension. During last years, multiple possible mechanisms involved in this association were identified. Adipose tissue has an important role in the genesis of hypertension in obese patients through several pathways: insulin resistance, leptin, renin-angiotensin-aldosteron system and mediators of inflammation (TNF-alpha, IL-6). Adipocyte may be the major player in the development of insulin resistance and hypertension, elements of the metabolic syndrome, responsible for the cardiovascular complications.

Topics: Adipocytes; Cytokines; Humans; Hypertension; Leptin; Metabolic Syndrome; Obesity; Renin-Angiotensin System

The dramatic increase in the prevalence of obesity is a global phenomenon associated with increased risk of the development of cardiovascular and renal disease. Changes in renal structure and function that occur early in the development of obesity may lead to urine outflow obstruction and increased intrarenal pressure, mechanisms sufficient to shift the pressure-natriuresis relation to higher blood pressure levels. Another important alteration that may lead to hypertension with obesity is the increase in sympathetic nervous system activity. Several studies point to higher leptin levels associated with hypertension in humans, and animal data now convincingly suggest that leptin has direct central effects that increase sympathetic outflow to the kidneys, associated with increases in blood pressure. Although understanding of the pathophysiology of obesity-associated hypertension has made substantial progress during the past years, treatment of obese hypertensives remains largely empirical and clearly deserves to be addressed in larger randomized, controlled trials.

Topics: Adipose Tissue; Animals; Antihypertensive Agents; Humans; Hypertension; Kidney; Leptin; Models, Animal; Obesity; Renin-Angiotensin System; Sympathetic Nervous System

Topics: Animals; Baroreflex; Blood Pressure; Cardiovascular Physiological Phenomena; Humans; Hypertension; Leptin; Models, Cardiovascular; Models, Neurological; Neurosecretory Systems; Rats; Sympathetic Nervous System

Obesity and arterial hypertension are important public health problems. Both overweight and hypertension predispose to cardiovascular diseases, such as myocardial infarction, stroke and renal failure. Moreover, overweight clearly predisposes to hypertension, and thus to an increased prevalence of cardiovascular diseases. This in turn favors inactivity and further weight gain, leading to an exacerbation of cardiovascular disorders. Obesity, hypertension and cardiovascular diseases thus contribute to three corners of a vicious triangle. It is within this conceptual framework that this paper reviews the pathogenesis of obesity-related hypertension, which is highly complex. Many factors act together to promote vasoconstriction and sodium retention. Leptin, free fatty acids and insulin, whose levels are increased in obesity, may act synergistically to stimulate sympathetic activity and vasoconstriction. In addition, obesity-induced insulin resistance and endothelial dysfunction may operate as amplifiers of the vasoconstrictor response. Finally, increased renal tubular reabsorption of sodium may also occur, caused by an increased renal sympathetic nerve activity, the direct effect of insulin, hyperactivity of the renin-angiotensin system and possibly by an alteration of intrarenal physical forces. All together, these factors will lead to sustained hypertension. Because the prevalence of obesity was steadily increasing in the last decades, leading to an increased prevalence of hypertension and cardiovascular disorders, obesity and hypertension will most likely become the health challenges of the twenty-first century.

Topics: Adult; Aged; Fatty Acids, Nonesterified; Humans; Hypertension; Insulin Resistance; Kidney; Leptin; Middle Aged; Obesity; Sodium; Sympathetic Nervous System; Tumor Necrosis Factor-alpha; Weight Gain

Topics: Adipose Tissue; Cardiovascular Diseases; Complement Factor D; Hormones, Ectopic; Humans; Hyperlipidemias; Hypertension; Intercellular Signaling Peptides and Proteins; Leptin; Obesity; Renin-Angiotensin System; Resistin; Serine Endopeptidases; Tumor Necrosis Factor-alpha

Obesity is the most common nutritional disorder in the United States. Growing evidence suggests that obesity initiates a cascade of disorders including hypertension, diabetes, atherosclerosis, and chronic renal disease, many of which are interdependent. Abnormal kidney function, caused by increased renal tubular reabsorption, initiates volume expansion and increased blood pressure during excess weight gain, and the hypertension and metabolic abnormalities associated with obesity, in turn, contribute to chronic renal disease. Obesity causes cardiac and vascular disease through well-known mediators such as hypertension, type II diabetes, and dyslipidemia, but there is evidence for less well-characterized mediators such as chronic inflammation and hypercoagulation. Although obesity is increasingly recognized as a serious health problem, there are still many unanswered questions about how the multiple disorders associated with excess weight gain interact to cause cardiovascular and renal disease. Also, there are few studies that have examined whether sustained weight loss in obese subjects can reverse these changes. In view of the "epidemic" of obesity in our country and the excess burden of cardiovascular and renal disease in minority populations, addressing these issues is of paramount importance for the Jackson Heart Study, as well as for other national health initiatives.

Topics: Animals; Blood Pressure; Cardiovascular Diseases; Humans; Hypertension; Kidney Diseases; Leptin; Models, Biological; Obesity

Topics: Animals; Bezafibrate; Biguanides; Fatty Acids, Nonesterified; Humans; Hyperglycemia; Hyperinsulinism; Hyperlipidemias; Hypertension; Hypoglycemic Agents; Hypolipidemic Agents; Insulin Resistance; Leptin; Life Style; Metabolic Syndrome; Pioglitazone; Thiazoles; Thiazolidinediones; Tumor Necrosis Factor-alpha

Recent studies demonstrate major effects of adrenal medullary and catecholaminergic pathways on a wide variety of normal physiologic and regulatory events. Alterations in these pathways, involving changes in catecholamines or in proteins and peptides costored and coreleased with catecholamines, may lead to profound changes in autonomic, cardiovascular, neuroendocrine, metabolic, nociceptive, and immune function. These findings have important implications for a variety of human disease states. In addition, molecules associated with catecholaminergic function may provide novel diagnostic and therapeutic strategies for human disease and suggest specific genetic loci as important and fruitful targets for further genetic and pharmacogenetic studies.

Topics: Catecholamines; Chromaffin Cells; Chromogranin A; Chromogranins; Dopamine beta-Hydroxylase; Humans; Hypertension; Leptin; Mutation; Nervous System Diseases; Parkinson Disease; Pheochromocytoma

Topics: Humans; Hypertension; Leptin; Obesity

The prevalence of obesity is rising at an alarming rate worldwide, with consequent increases in type 2 diabetes, hypertension and cardiovascular morbidity and mortality. Central neural mechanisms, via the activation of the sympathetic nervous system may contribute to obesity-related cardiovascular diseases through the promotion of hypertension, dysrhythmia and atherosclerosis. However, the mechanisms responsible for this sympatho activation have not been identified. Leptin is an adipocyte-derived hormone that promotes weight loss by reducing appetite and by increasing energy expenditure through sympathetic stimulation to thermogenic tissue. Leptin also produces sympathoactivation to kidneys, hindlimb and adrenal glands, suggesting that the obesity-associated increase in sympathetic nerve activity could be due in part to these sympathetic effects of leptin. However, most human obesity appears to be associated with leptin resistance. Recent studies indicate that leptin resistance may be selective, with preservation of adverse sympathetic effects despite the loss of the metabolic actions of leptin. The leptin receptor is expressed in several hypothalamic nuclei including the arcuate nucleus. The melanocortin system, neuropeptide Y and corticotrophin-releasing factor have emerged as principal neuropeptide mediators of leptin action in the arcuate nucleus. These neuropeptides exert varying effects by different pathways. Several other candidate hypothalamic pathways that can mediate the effects of leptin have been identified. The understanding of neuronal signaling pathways involved in leptin signaling and energy balance has opened new research possibilities for the treatment of obesity.

Topics: Animals; Anti-Obesity Agents; Brain; Drug Resistance; Humans; Hypertension; Hypothalamus; Leptin; Neuropeptide Y; Obesity; Receptors, Cell Surface; Receptors, Corticotropin; Receptors, Leptin; Receptors, Melanocortin; Receptors, Neuropeptide Y; Sympathetic Nervous System

Heightened sympathetic nervous system activity, hyperinsulinemia, insulin resistance, and hyperleptinemia contribute to obesity-related hypertension. However, the precise mechanism and sequence of events in this pathophysiologic event have not been clarified. This review concentrates on studies helping to clarify the mechanisms of blood pressure elevation associated with weight change, concentrating on the temporal changes in neuroendocrine factors that are known to control energy metabolism and blood pressure. A better understanding of the pathophysiologic mechanisms of obesity-related hypertension may help in prevention, treatment, and slowing of the cardiovascular complications of obesity.

Topics: Blood Pressure; Body Weight; Exercise; Feeding Behavior; Humans; Hypertension; Insulin; Japan; Leptin; Neurotransmitter Agents; Obesity; Risk Factors; Sweden; Sympathetic Nervous System

Several studies have shown the association between obesity and hypertension. The pathophysiologic mechanisms of obesity-related hypertension remain unknown. Clinical and experimental studies have shown that obesity is associated with enhanced sympathetic nervous activity. Thus, sympathetic nerve activation seems to play a major role in obesity-associated hypertension. However, the factors responsible for this sympathoactivation have not been identified. Leptin is an adipocyte-derived hormone that promotes weight loss by reducing appetite and food intake and by increasing energy expenditure through sympathetic stimulation to brown adipose tissue. Leptin also produces sympathoactivation to kidneys, hindlimb, and adrenal glands, indicating that the obesity-associated increase in sympathetic nerve activity could be due in part to these sympathetic effects of leptin. However, obesity is associated with leptin resistance, since high circulating levels of leptin were observed in obese subjects. Recent evidences indicate that this leptin resistance could be selective with preservation of sympathetic effects despite the loss of metabolic action of leptin. This suggests divergent central pathways underlying metabolic and sympathetic effects of leptin. Several neuropeptides have emerged as potent candidate mediators of leptin action in the central nervous system, including the melanocortin system, neuropeptide Y, and cortico-trophin releasing factor. A detailed understanding of the multitude and complexity of integrated neuronal circuits and neuropeptide-containing pathways in leptin action will help in understanding the pathogenesis of obesity and related disorders.

Topics: Animals; Cardiovascular System; Humans; Hypertension; Hypothalamus; Leptin; Neuropeptide Y; Obesity; Sympathomimetics

Obesity results from an imbalance between caloric intake and energy expenditure. Twin, adoption, and family studies have not only shown that genetic factors play an important role in the pathogenesis of obesity, but also contribute to several comorbidities including hypertension and type 2 diabetes. In recent years, several single-gene defects responsible for obesity in rodents and, in rare cases, of human obesity have been identified. Besides leptin as the most notable example, numerous other proteins and neuropeptides have recently been found that participate in a complex network to regulate food intake and energy expenditure. Interestingly, some of these molecules may also play a role in the development of obesity-related hypertension. The ongoing search for relevant genetic variants should result in a better understanding of energy metabolism and hopefully clarify molecular mechanisms underlying the association between obesity and related comorbidities. This knowledge should help develop new strategies for the treatment of obesity and associated risk factors for hypertension and related cardiovascular disorders.

Topics: Energy Metabolism; Humans; Hypertension; Leptin; Neuropeptides; Obesity; Receptors, Adrenergic, beta-3

Topics: Animals; Crosses, Genetic; Diabetes Mellitus; Food Deprivation; Glucose; Humans; Hypertension; Insulin; Leptin; Male; Mice; Mice, Transgenic; Obesity

Insulin resistance and hyperinsulinemia have been observed in essential hypertension. The selective impairment of glucose metabolism in skeletal muscle may accompanied hyperinsulinemia and raise blood pressure through sympathetic nervous system and/or renin-angiotensin system activation, renal sodium retention, proliferation of vascular smooth muscle and leptin. Recently, molecular techniques have applied for investigating the mechanisms of insulin resistance. The mutation of insulin receptor gene, changes of muscle fiber composition and muscle blood flow, abnormalities of insulin signal transduction, and TNF-alpha are considered as involvement of insulin resistance in the skeletal muscle. While further study will be necessary to clarify the mechanisms of insulin resistance and hypertension.

Topics: Animals; Cell Division; Glucose; Humans; Hyperinsulinism; Hypertension; Insulin Resistance; Leptin; Muscle, Skeletal; Muscle, Smooth, Vascular; Receptor, IGF Type 1; Receptor, Insulin; Renin-Angiotensin System; Signal Transduction; Sodium-Potassium-Exchanging ATPase; Sympathetic Nervous System; Syndrome; Tumor Necrosis Factor-alpha

Obesity is often accompanied with hypertension and increases cardiovascular events. Japanese new guideline on identification of obesity includes a modified BMI categories and a method of detection of visceral fat obesity in Japanese. Hyper-insulinemia and leptin released from adipose tissue play an important role in the development of hypertension in obese patients. Insulin and leptin increase sympathetic tone which results in sodium retention and hyper-responsiveness of blood vessels. As leptin has also a direct vasodilative and diuretic action, its effect on blood pressure is bidirectional. Life style modification, especially diet and physical exercise are important to obtain the body weight loss and the improvement of insulin resistance. Dynamic exercise at the level of fifty percent of max VO2 for 30 to 60 minutes over three times a week should be recommended for hypertensive patients with obesity. ACE inhibitors improve the hypersympathetic tone and impaired insulin sensitivity in obese patients. Calcium antagonist is also useful for these patients.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Diet; Exercise; Humans; Hyperinsulinism; Hypertension; Insulin; Leptin; Life Style; Obesity; Practice Guidelines as Topic

Obesity may account for as much as 65% to 75% of human essential hypertension in most industrialized countries. Excess renal sodium reabsorption and a hypertensive shift of renal-pressure natriuresis play a key role in mediating obesity hypertension. Sympathetic activation contributes to obesity-induced sodium retention and hypertension because adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with other neurochemical pathways in the hypothalamus may be a partial link between excess weight gain and increased sympathetic activity. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term intravenous leptin infusions in nonobese rodents at rates that raise plasma concentrations to the levels found in severe obesity increase arterial pressure and heart rate through adrenergic activation. Also, transgenic mice that overexpress leptin develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including melanocortin-4 receptors. However, it is unclear whether this pathway or others, such as neuropeptide Y, mediate the long-term effects of leptin on blood pressure. In addition, leptin has other actions, such as stimulation of nitric oxide formation and enhancement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the precise role of these complex interactions in human obesity has not been elucidated, this is an important area for further investigation, especially considering the current epidemic of obesity in most industrialized countries.

Topics: Animals; Cardiovascular System; Humans; Hypertension; Kidney; Leptin; Obesity; Sympathetic Nervous System

The first unifying definition for the metabolic syndrome was proposed by WHO in 1998. In accordance to this, patients with type 2 diabetes mellitus or impaired glucose tolerance have the syndrome if they fulfil two of the criteria: hypertension, dyslipidaemia, obesity/abdominal obesity and microalbuminuria. Persons with normal glucose tolerance (NGT) should also be insulin resistant. About 40% of persons with impaired glucose tolerance (IGT) and 70% of patients with type 2 diabetes have features of the syndrome. Importantly, presence of the dysmetabolic syndrome is associated with reduced survival, particularly because of increased cardiovascular mortality. The dysmetabolic syndrome most likely results from interplay between several genes and an affluent environment. Compatible with the thrifty gene theory, common variants in genes regulating lipolysis, thermogenesis and glucose uptake in skeletal muscle account for a large part of such thrifty genes. However, hitherto unknown genes may still be identified by random gene approaches.

Topics: Abdomen; Adult; Age Distribution; Aged; Animals; Carrier Proteins; Diabetes Mellitus, Type 2; Genotype; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Leptin; Middle Aged; Mutation; Obesity; Phenotype; Prevalence; Pro-Opiomelanocortin; Receptor, Melanocortin, Type 4; Receptors, Cell Surface; Receptors, Leptin; Receptors, Peptide; Syndrome

Classical gene targeting has identified many genes important for fetal and placental development. Null mutation of these genes may lead to fetal growth restriction, malformation or embryonic death. Growth restriction of epigenetic basis can predispose to adult-onset diseases. The mechanisms underlying this process, termed 'fetal programming', are beginning to be understood.

Topics: Animals; Cardiovascular System; Embryonic and Fetal Development; Endocrine System; Female; Fetal Growth Retardation; Genetic Techniques; Glucocorticoids; Humans; Hypertension; Insulin-Like Growth Factor I; Insulin-Like Growth Factor II; Leptin; Mice; Placenta; Pregnancy

Insulin resistance syndrome is the theory that glucose intolerance, hyperinsulinemia, increased very low density lipoprotein triglyceride level, decreased high density lipoprotein cholesterol level, and hypertension are proposed consequences of insulin resistance. These metabolic disturbances have been shown to increase the risk of coronary artery disease. In this theory, insulin resistance and the resultant hyperinsulinemia are considered to raise blood pressure through 1) sympathetic nervous system activation, 2) renal sodium retention, 3) renin-angiotensin system stimulation, and 4) intracellular calcium accumulation in vascular smooth muscle. Indeed, metabolic disturbance and insulin resistance have been pointed out in essential hypertensives. Leptin is a recently discovered hormone produced by an adipocyte-specific ob gene, that contributes to the regulation of energy balance by informing the hypothalamus of the amount of adipose tissue in the body. As a result, the hypothalamus adjusts food intake, thermogenesis, and energy expenditure appropriately. It was clarified that ob gene expression and plasma leptin level in humans were highly correlated with the body mass index, insulin sensitivity and blood pressure. Thus, leptin could play a role in the pathophysiology of insulin-resistant hypertension.

Topics: Coronary Disease; Glucose Intolerance; Humans; Hyperinsulinism; Hyperlipidemias; Hypertension; Hypothalamus; Insulin Resistance; Leptin; Risk; Syndrome

Obesity is the most common cause of human essential hypertension in most industrialized countries. Although the precise mechanisms of obesity hypertension are not fully understood, considerable evidence suggests that excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role. Sympathetic activation appears to mediate at least part of the obesity-induced sodium retention and hypertension since adrenergic blockade or renal denervation markedly attenuates these changes. Recent observations suggest that leptin and its multiple interactions with neuropeptides in the hypothalamus may link excess weight gain with increased sympathetic activity. Leptin is produced mainly in adipocytes and is believed to regulate energy balance by acting on the hypothalamus to reduce food intake and to increase energy expenditure via sympathetic activation. Short-term administration of leptin into the cerebral ventricles increases renal sympathetic activity, and long-term leptin infusion at rates that mimic plasma concentrations found in obesity raises arterial pressure and heart rate via adrenergic activation in non-obese rodents. Transgenic mice overexpressing leptin also develop hypertension. Acute studies suggest that the renal sympathetic effects of leptin may depend on interactions with other neurochemical pathways in the hypothalamus, including the melanocortin-4 receptor (MC4-R). However, the role of this pathway in mediating the long-term effects of leptin on blood pressure is unclear. Also, it is uncertain whether there is resistance to the chronic renal sympathetic and blood pressure effects of leptin in obese subjects. In addition, leptin also has other cardiovascular and renal actions, such as stimulation of nitric oxide formation and improvement of insulin sensitivity, which may tend to reduce blood pressure in some conditions. Although the role of these mechanisms in human obesity has not been elucidated, this remains a fruitful area for further investigation, especially in view of the current "epidemic" of obesity in most industrialized countries.

Topics: Animals; Blood Pressure; Body Mass Index; Coronary Circulation; Disease Models, Animal; Dogs; Fatty Acids; Humans; Hypertension; Kidney; Leptin; Natriuresis; Neuropeptides; Obesity; Sodium; Sympathetic Nervous System

The clustering of cardiovascular risk factors such as abdominal obesity, hypertension, dyslipidaemia and glucose intolerance in the same persons has been called the metabolic or insulin-resistance syndrome. In 1998 WHO proposed a unifying definition for the syndrome and chose to call it the metabolic syndrome rather than the insulin-resistance syndrome. Although insulin resistance has been considered as a common denominator for the different components of the syndrome, there is still debate as to whether it is pathogenically involved in all of the different components of the syndrome. Clustering of the syndrome in families suggests a genetic component. It is plausible that so-called thrifty genes, which have ensured optimal storage of energy during periods of fasting, could contribute to the phenotype of the metabolic syndrome. Common variants in a number of candidate genes influencing fat and glucose metabolism can probably, together with environmental triggers, increase susceptibility to the syndrome. Among these, the genes for beta 3-adrenergic receptor, hormone-sensitive lipase, lipoprotein lipase, IRS-1, PC-1, skeletal muscle glycogen synthase, etc. appear to increase the risk of the metabolic syndrome. In addition, novel genes may be identified by genome-wide searches.

Topics: Carrier Proteins; Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Genetic Predisposition to Disease; Glycogen Synthase; Humans; Hypertension; Insulin Resistance; Leptin; Male; Obesity; Receptors, Adrenergic, beta; Receptors, Cell Surface; Receptors, Cytoplasmic and Nuclear; Receptors, Leptin; Transcription Factors

Topics: Adipose Tissue; Animals; Diabetes Mellitus, Type 2; Gene Expression; Humans; Hypertension; Leptin; Obesity; Signal Transduction

Topics: Animals; Blood Pressure; Humans; Hypertension; Insulin; Kidney Tubules; Leptin; Renin-Angiotensin System; Sodium; Sympathetic Nervous System

Topics: Animals; Blood Pressure; Female; Glucose; Humans; Hypertension; Hypogonadism; Leptin; Mice; Mice, Transgenic; Obesity; Sympathetic Nervous System

Hypertension results from a complex and diverse array of metabolic and physiologic processes that interact with environmental factors to ultimately determine blood pressure levels and disease. Consequently, the identification of genes related to hypertension is complicated by the heterogeneity of its etiology and the likelihood that several genes with moderate effects, possibly acting in a context-dependent manner, influence blood pressure and the occurrence of hypertension. A number of studies have recently implicated variation within the beta(2)-adrenergic receptor in blood pressure regulation and the development of hypertension. The role of these findings is reviewed here, and their possible clinical implications in human hypertension.

Topics: Animals; Comorbidity; Humans; Hypertension; Leptin; Male; Mice; Mice, Transgenic; Obesity; Polymorphism, Genetic; Receptors, Adrenergic, beta-2

Excess weight gain is a major cause of essential hypertension, and abnormal kidney function appears to be a cause as well as a consequence of obesity hypertension. Excess renal sodium reabsorption and a hypertensive shift of pressure natriuresis play a major role in mediating increased blood pressure associated with weight gain. Activation of the renin-angiotensin and sympathetic nervous systems and physical compression of the kidneys appear to contribute to obesity-induced increases in sodium reabsorption and hypertension.

Topics: Fatty Acids; Hemodynamics; Humans; Hypertension; Kidney; Leptin; Natriuresis; Obesity; Renin-Angiotensin System; Sodium; Sympathetic Nervous System

Leptin is a protein produced by adipose tissue that acts in the central nervous system (CNS) to decrease appetite and increase energy expenditure. Leptin thus functions as the afferent component of a negative feedback loop that maintains stable adipose tissue mass. Intravenous leptin increases norepinephrine turnover and sympathetic nerve activity to thermogenic brown adipose tissue. Leptin also increases sympathetic nerve activity to tissues not usually considered thermogenic, including the kidney, hindlimb, and adrenal gland. Chronic systemic CNS administration of leptin increases arterial pressure and heart rate in conscious animals. However, leptin has additional cardiovascular actions that may act to oppose sympathetically mediated vasoconstriction. These actions include natriuresis, insulin sensitization, endothelium-dependent dilatation, and angiogenesis. Thus, the overall effect of leptin on arterial pressure has been unclear. Recent studies have demonstrated that leptin-deficient ob/ob obese mice have lower arterial pressure than lean controls with normal leptin levels. These studies suggest that leptin contributes physiologically to maintenance of arterial pressure. Leptin expression and plasma leptin concentrations are elevated in obese humans. Abnormalities in the generation or actions of leptin may, therefore, have implications for the sympathetic, cardiovascular, and renal changes associated with obesity.

Topics: Adipose Tissue; Adrenal Glands; Adrenergic alpha-Agonists; Animals; Appetite; Blood Pressure; Brain; Energy Metabolism; Heart Rate; Humans; Hypertension; Kidney; Leptin; Mice; Mice, Obese; Norepinephrine; Obesity; Sympathetic Nervous System; Vasodilator Agents

Atherosclerosis starts in childhood, and is accelerated in some individuals. A cluster of clinical and biochemical factors constitute the risk profile for many of them, perhaps most important being metabolic insulin resistance syndrome. Insulin resistance and its components for children and adolescents, especially obesity and dyslipidemia, are generators of hypertension, glucose intolerance and complications of atherosclerosis in adulthood. Some individuals are genetically predisposed, particularly those with the family history of such disorders. For many subjects, there is 'tracking' of metabolic and lifestyle factors from early age to adulthood. Several new risk factors of atherosclerosis (e.g. level of lipoprotein (a), procoagulant state, hyperhomocysteinemia, low birth weight and adverse in-utero environment, and possibly inflammatory markers) are current and potentially future areas of research concerning children and young individuals. Definition of and research on new and hitherto not investigated factors and formulation of strategies to neutralize the known factors are of paramount importance for primary prevention of atherosclerosis. Simple and effective measures for prevention include increasing awareness of the diseases, maintenance of ideal body weight, regular physical exercise, avoidance of smoking and chewing of tobacco, eating a balanced diet, and early periodic monitoring of blood pressure and metabolic status. These measures, starting from childhood, should be applied to all and in particular to the susceptible offspring, predisposed individuals, and populations.

Topics: Adolescent; Adult; Age Factors; Arteriosclerosis; Birth Weight; Blood Coagulation Factors; Child; Child, Preschool; Coronary Disease; Diabetes Complications; Exercise; Female; Homocysteine; Humans; Hypertension; Infant; Infant, Newborn; Insulin Resistance; Leptin; Life Style; Lipids; Lipoprotein(a); Male; Middle Aged; Obesity; Primary Prevention; Risk Factors; Sex Factors; Smoking

Topics: Animals; Hypertension; Leptin; Mice; Mice, Obese

Longitudinal and cross-sectional studies suggest that a large number of obese patients have a high prevalence of hypertension. This association causes the following changes: insulin and leptin resistance with a suppressed biologic activity of natriuretic peptide, which contributes to sodium retention with concomitant expanded cardiopulmonary volume and increased cardiac output. The cellular metabolism of cations may be altered in obesity and may lead to changes in vascular responsiveness and increased vascular resistance. These changes lead to structural adaptations in the heart characterized by concentric-eccentric left ventricular hypertrophy. The hypertrophic condition provides the basis for the development of congestive heart failure and cardiac arrhythmias that may explain the higher rates of cardiac sudden death in those patients. In the kidneys, obesity hypertension may initiate a derangement of renal function. The increased deposit of interstitial cells and of extracellular matrix between the tubules induces higher interstitial hydrostatic pressure and tubular sodium reabsorption. The consequent increase in renal flow and glomerular filtration enhances albuminuria excretion and the susceptibility to the development of renal damage. In summary, the hemodynamic and structural adaptations related to obesity hypertension is the cause of greater risk for adverse cardiovascular and renal events.

Topics: Animals; Cardiovascular System; Humans; Hypertension; Kidney; Leptin; Natriuretic Agents; Obesity

offsity is associated with an increased risk of hypertension. In the past 5 years there have been dramatic advances into the genetic and neurobiological mechanisms of obesity with the discovery of leptin and novel neuropeptide pathways regulating appetite and metabolism. In this brief review, we argue that these mounting advances into the neurobiology of obesity have and will continue to provide new insights into the regulation of arterial pressure in obesity. We focus our comments on the sympathetic, vascular, and renal mechanisms of leptin and melanocortin receptor agonists and on the regulation of arterial pressure in rodent models of genetic obesity. We suggest 3 concepts. First, the effect of obesity on blood pressure may depend critically on the genetic-neurobiological mechanisms underlying the obesity. Second, obesity is not consistently associated with increased blood pressure, at least in rodent models. Third, the blood pressure response to obesity may be critically influenced by modifying alleles in the genetic background.

Topics: Animals; Appetite; Carrier Proteins; Humans; Hypertension; Leptin; Neuropeptides; Obesity; Proteins; Receptor, Melanocortin, Type 4; Receptors, Cell Surface; Receptors, Corticotropin; Receptors, Leptin; Risk Factors

The article summarizes the endocrinology axis in relation to leptin in the obesity. There is a glucocorticoid hypothesis in the obesity origin. Human plasma leptin levels are elevated in Cushing's syndrome and there is a robust leptin secretory responses to dexamethasone. Obesity impacts on reproductive function in man and women. Leptin levels are higher in women than in men and a critical blood leptin level is necessary to trigger reproductive ability in women. The relationship between body mass index and circulating leptin varies during the course of spontaneous cycles in women, the best correlation occurring during the luteal phase when progesterone and leptin concentrations are highest. Obesity is associated with a decrease in growth hormone (GH) and reversible with weight loss. The influence of body composition on GH secretion in the obesity may be mediated through leptin, acting as a peripheral signal from adipose tissue. Thyroid dysfunction appear not associated with alterations in serum leptin levels. There is a significant relationship between insulin and leptin, but it is not immediate, since type 2 diabetics show similar leptin levels to those of nondiabetic humans of the same body mass index.

Topics: Adult; Animals; Body Mass Index; Cushing Syndrome; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Human Growth Hormone; Humans; Hyperinsulinism; Hypertension; Hypothalamo-Hypophyseal System; Insulin; Leptin; Male; Menstrual Cycle; Mice; Mice, Obese; Middle Aged; Obesity; Pituitary-Adrenal System; Progesterone; Rats; Reproduction; Sex Factors

The combination of obesity with arterial hypertension is frequent finding in clinical practice. In 70% of the males and 61% of the females the high blood pressure is directly connected with obesity. The assumed mechanisms by which obesity leads to arterial hypertension are: insuline resistance; genetic factors (hypothesis for the sparing gene); correlations leptin-neuropeptide Y; fatty tissue as origin of local pressor and depressor humoral factors. The arterial hypertension in obesity is salt-sensible, associated with increased intraglomerular pressure, microalbuminuria and increased risk for cardiovascular complications. The reduction of the body weight is the principal nonmedical mean for treatment of the arterial hypertension. Of the antihypertensive drugs those which are neutral with respect to the carbohydrat and fat metabolism are preferred inhibitors of the converting enzyme, calcium antagonists, selective alpha-1 blockers, central alpha-2 agonist.

Topics: Adipose Tissue; Cardiovascular Diseases; Humans; Hypertension; Insulin Resistance; Leptin; Obesity; Risk Factors

Structural and functional properties of the left ventricle (LV) wall have been reported to be altered in hypertension, even at early stages of the disease. Abnormal adipokine levels affect blood pressure regulation. Hypo-adiponectinaemia and hyper-leptinaemia were reported in hypertension.. To evaluate the effects of valsartan versus amlodipine on LV deformation also, on plasma adiponectin and leptin levels in hypertensive individuals.. LV strain was measured by two-dimensional speckle tracking echocardiography, plasma levels of adiponectin and leptin was determined in 30 healthy individuals served as control group and in 200 hypertensive patients before and after treatment for 6 months with either valsartan 160 mg or amlodipine 10 mg.. Compared to control group longitudinal strain was significantly affected in hypertensive patients, adiponectin was significantly lower while TNF-α, hs-CRP and leptin levels were significantly higher in hypertensive group. A significant improvement in LV functions, along with a decrease in leptin and increase in adiponectin levels in valsartan group compared to amlodipine group.. Our results indicate that valsartan is superior to amlodipine when it comes to affecting the hormonal function of human adipose tissue. Valsartan has a beneficial effect on LV deformation and function presented in GLS.

Topics: Adipokines; Adiponectin; Adult; Amlodipine; Angiotensin II Type 1 Receptor Blockers; Antihypertensive Agents; Biomarkers; C-Reactive Protein; Calcium Channel Blockers; Echocardiography; Egypt; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Predictive Value of Tests; Time Factors; Treatment Outcome; Tumor Necrosis Factor-alpha; Valsartan; Ventricular Function, Left; Ventricular Remodeling

The aim of the study was to assess the impact of individualised nutritional intervention based on the DASH diet (Dietary Approaches to Stop Hypertension) on the nutritional status, blood pressure, and selected biochemical parameters of obese/overweight patients with primary arterial hypertension.. A total of 131 participants were randomised to the DASH intervention group (DIG; n = 69, 33 males) or the control group (CG; n = 62, 32 males). A three-month nutritional intervention was carried out in the DIG group, while the control group received only standard recommendations. Body weight, height, waist and hip circumference, body composition, blood pressure, serum glucose, and insulin and leptin concentrations were measured at the baseline and after the intervention.. Sixty-four (92.8%) participants in the intervention and 62 (100%) in the control group completed the study. In the DIG group a significant decrease in body mass, systolic and diastolic blood pressure, body fat content, fasting glucose, insulin, and leptin concentrations were observed in comparison to the control group (p < 0.05).. The DASH dietary intervention provides significant benefits to overweight/obese patients with primary hypertension.

Topics: Aged; Blood Glucose; Blood Pressure; Body Composition; Dietary Approaches To Stop Hypertension; Female; Humans; Hypertension; Insulin; Leptin; Male; Middle Aged; Overweight; Prospective Studies

Metabolic syndrome (MetS) is associated with diabetes mellitus and cardiovascular diseases. Our previous study indicated that people with MetS showed a decrease in waist circumference and a decreasing trend in blood pressure after 1-year yoga. This study investigated the effect of yoga on MetS people with high-normal blood pressure by exploring modulations in proinflammatory adipokines (leptin, chemerin, visfatin, and plasminogen activator inhibitor-1 or PAI-1) and an anti-inflammatory adipokine (adiponectin). A total of 97 Hong Kong Chinese individuals aged 57.6 ± 9.1 years with MetS and high-normal blood pressure were randomly assigned to control (n = 45) and yoga groups (n = 52). Participants in the control group were not given any intervention but were contacted monthly to monitor their health status. Participants in the yoga group underwent a yoga training program with three 1-hour yoga sessions weekly for 1 year. The participants' sera were harvested and assessed for adipokines. Generalized estimating equation (GEE) was used to examine the interaction effect between 1-year time (pre vs post), and intervention (control vs yoga). GEE analyses revealed significant interaction effects between 1-year time and yoga intervention for the decreases in leptin and chemerin and the increase in adiponectin concentration in the sera examined. These results demonstrated that 1-year yoga training decreased proinflammatory adipokines and increased anti-inflammatory adipokine in adults with MetS and high-normal blood pressure. These findings support the beneficial role of yoga in managing MetS by favorably modulating adipokines.

Topics: Adipokines; Aged; Chemokines; Female; Humans; Hypertension; Intercellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Plasminogen Activator Inhibitor 1; Risk Factors; Yoga

Leptin is associated to the lack of blood pressure control as well as target organ damage in resistant hypertensive (RH) subjects. Single-nucleotide polymorphisms (SNPs) rs7799039 and rs1137101 in leptin (LEP) and leptin receptor (LEPR) genes, respectively, are associated with cardiovascular disease and metabolic syndrome. We evaluated the association of these two SNPs with clinical and biochemical features in 109 apparent treatment-RH subjects (aTRH) and 125 controlled hypertensives. Homozygous genotypes GG (n = 43) vs. AA (n = 14) for rs7799039 and AA (n = 34) vs. GG (n = 26) genotypes for rs1137101 were compared in aTRH subjects. There was no difference in leptin levels among both SNPs. On the other hand, LEP SNP (GG vs. AA) associated with the levels of glycated haemoglobin (6.4 ± 1.4 vs. 7.8 ± 2.3%, p = 0.03), insulin (8.6 ± 4.6 vs. 30.6 ± 27.7 uUI/mL, p = 0.01), HDL-cholesterol (51 ± 16 vs. 39 ± 11 mg/dL, p = 0.001) and PWV (9.5 ± 2.1 vs. 11.2 ± 2.8 m/s, p = 0.03). LEPR SNP (AA vs. GG), associated with heart rate (69 ± 12 vs. 67 ± 12 bpm, p = 0.03), fat mass (31 ± 11 vs. 24 ± 8 kg, p = 0.03) and triglycerides levels (175 ± 69 vs. 135 ± 75 mg/dL, p = 0.03). These findings may be clinically useful for identifying a group of aTRH who may have a LEP and/or LEPR gene variants, which may predispose this specific group to worse or better outcomes.

Topics: Aged; Cross-Sectional Studies; Drug Resistance; Female; Follow-Up Studies; Humans; Hypertension; Leptin; Male; Middle Aged; Polymorphism, Single Nucleotide; Quantitative Trait, Heritable; Receptors, Leptin

Severe underweight may be a risk factor for hypertension in developing countries, although the manner whereby this occurs is unknown. Leptin is known to exert both beneficial and detrimental vascular effects, and is predictive of poor cardiovascular outcome at high levels, but also at low levels. We explored the relationship between blood pressure and leptin in black men from South Africa with a body mass index (BMI) in the underweight to normal range. We included 113 African men (BMI≤25 kg/m(2)) and took anthropometric, biochemical and cardiovascular measures. The blood pressure-leptin relationship was then investigated along quintiles of leptin and within BMI stratified median split (20 kg/m(2)) groups. Blood pressure increased across leptin quintiles 1-3 (p for trend≤0.040), whereas no relationship was observed along quintiles 3 to 5 (p for trend≥0.14) (adjusted for age and waist circumference). Blood pressure was similar in the two BMI median split groups (p≥0.083). In the low BMI group only, blood pressure associated positively with leptin following unadjusted, partial, and full adjustment (systolic blood pressure and diastolic blood pressure: R(2)=0.20-0.27, β=0.32-0.34, p≤0.009). Decreasing leptin levels are not likely to contribute to hypertension prevalence in the underweight. Rather, in African men with a BMI≤20 kg/m(2), low leptin levels are positively and independently associated with elevated blood pressure, which is not seen at higher BMI (20-25 kg/m(2)). Our findings suggest a differential concentration dependent vascular effect of leptin in underweight and normal weight African men.

Topics: Adult; Aged; Black People; Blood Pressure; Body Mass Index; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Prevalence; South Africa

Epidemiological studies have suggested that the daily intake of flavonoids is associated with a decreased risk of developing cardiovascular disease. Our purpose was to evaluate the effect of the addition of dietary flavonoids (DF) to antihypertensive treatment (AHT), based on telmisartan (Tms) or captopril (Cpr), on blood pressure (BP), body mass index (BMI), waist/hip ratio, leptin, lipid profile and inflammation in hypertensive young patients. An open-label, randomized, controlled trial was performed among 79 patients aged 20-55 years with grade I or grade II systemic arterial hypertension. The subjects were assigned to one of four groups for AHT plus DF during 6 months: Cpr (n = 14), Cpr + DF (n = 19), Tms (n = 25) and Tms + DF (n = 21). DF consisted of dark chocolate, dehydrated red apple and green tea in an infusion to obtain a daily dose of 425.8 ± 13.9 mg epicatechin equivalents. The BP and anthropometric parameters were measured every 2 weeks. Lipid profile, leptin and hsCRP were determined by standard methods. The combination AHT-DF produced an additional and significant reduction in (i) SBP/DBP of -5/-4 mmHg, being -7/-5 for Cpr + DF and -4/-3 for Tms + DF; (ii) triglyceride levels (-30.6%) versus AHT alone (-9.6%); and (iii) leptin: Cpr + DF versus Tms + DF (p < 0.005). Finally, C-reactive protein plasma levels were reduced significantly in all groups independently of the applied treatment. We conclude that the addition of flavonoids to pharmacological antihypertensive therapy shows additional benefits on BP, lipid profile, leptin, obesity and inflammation.

Topics: Adult; Antihypertensive Agents; Benzimidazoles; Benzoates; Biomarkers; Blood Pressure; C-Reactive Protein; Cacao; Candy; Captopril; Combined Modality Therapy; Diet; Female; Flavonoids; Fruit; Humans; Hypertension; Leptin; Lipids; Male; Malus; Mexico; Middle Aged; Tea; Telmisartan; Time Factors; Treatment Outcome; Young Adult

This study aimed to analyze the influence of H. pylori infection on insulin resistance and metabolic syndrome (MS) by multivariate analysis of a community-based cohort study. From January 2013 to February 2014,811 subjects were enrolled in a community-based cohort study from the northeastern region of Taiwan. All subjects received a demographic survey and blood tests, including an H. pylori antibody test, liver biochemistry tests, lipid profiles, sugar/insulin levels for Homeostatic model assessment (HOMA-IR index), and measurements of adipokines and inflammatory cytokines. A total of 264 men and 547 women were included in this study. The mean age was 59.2 ± 12.7 years. Subjects seropositive for H. pylori antibodies exhibited higher rates of hypertension, an increased incidence of a HOMA-IR index > 2.5 and a higher level of tumor necrosis factor-α than those without H. pylori antibodies. We found a significant difference in the presence of H. pylori antibodies between subjects with MS and those without MS (76.7% vs. 53.7%, p = 0.007) among subjects < 50 y/o. A HOMA-IR index >2.5, H. pylori antibody presence and leptin were predictors for MS in subjects < 50 y/o. The estimated odds ratio of MS for a subject with H. pylori antibodies was 3.717 (95% CI = 1.086-12.719) times that of a subject without H. pylori antibodies. In addition, no difference in H. pylori antibody status was detected for MS prediction in subjects that were ≧ 50 y/o (p = 0.861). In conclusion, subjects with H. pylori antibodies had a higher incidence of a HOMA-IR >2.5 than those without H pylori antibodies. For subjects aged < 50 y/o, the H. pylori antibody was a predictor for MS.

Topics: Age Factors; Aged; Antibodies, Bacterial; Case-Control Studies; Female; Helicobacter Infections; Helicobacter pylori; Humans; Hypertension; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Taiwan

Activation of the renin-angiotensin-aldosterone system (RAAS) and abnormal adipokine levels are biological alterations that affect blood pressure regulation and interact to link hypertension, obesity and metabolic diseases. While imbalanced levels of hormones produced by adipocytes including hypo-adiponectinaemia and hyperleptinaemia were reported in hypertension, little is known about how antihypertensive therapy affects these alterations. This study aimed to evaluate the effects of enalapril on plasma adiponectin and leptin levels in hypertensive individuals. Thirty-seven untreated hypertensive patients were prospectively treated with enalapril for 8 weeks. Blood samples were collected at baseline and after the treatment with enalapril. Plasma adiponectin and leptin levels were measured by enzyme-linked immunoassay. We found significant increases in adiponectin levels after enalapril treatment (5.4 ± 3.7 versus 6.0 ± 4.5 μg/mL, mean ± S.D., p = 0.04). Conversely, leptin levels were unchanged (18.0 ± 14.7 versus 18.4 ± 14.8 ng/mL, mean ± S.D., p = 0.31). Multiple linear regression revealed that baseline leptin is a significant predictor of systolic blood pressure reduction (β=0.269, p = 0.01) in hypertensive individuals treated with enalapril. While enalapril increases adiponectin levels in hypertensive individuals, baseline leptin levels predict blood pressure reduction in response to this therapy. These findings support the idea of an important relationship between RAAS and adipose tissue in hypertension and suggest that enalapril improves the adipokine profile, possibly allowing beneficial effects to overweight or obese hypertensive individuals.

Topics: Adiponectin; Adult; Angiotensin-Converting Enzyme Inhibitors; Enalapril; Essential Hypertension; Female; Humans; Hypertension; Leptin; Linear Models; Male; Middle Aged; Prospective Studies

Multiple epidemiological studies have shown that low testosterone levels are associated with and predict the future development of type 2 diabetes mellitus and the metabolic syndrome. The aim of our study was to show the influence of testosterone replacement therapy on obesity, HbA1c level, hypertension and dyslipidemia in patients with diabetes mellitus and androgen deficiency.. One hundred and twenty-five male patients with diabetes mellitus were screened; 85 subjects aged 41 to 65 years, with BMI from 27.0 to 48.0 kg/m(2), were randomized in a placebo-controlled study. They also underwent a routine physical examination and selected by free testosterone examination. We divided patients into two groups: 1) treatment group, where we used diet, physical activity, patient's antidiabetic therapy and testosterone replacement therapy; 2) placebo group, where we used diet, physical activity, patient's antidiabetic therapy and placebo.. After 6 months of treatment we repeated the diagnostic assessments: lipid profile was improved in both groups but in first group it was clinically significant. Free testosterone level increased in all groups, but in group I was clinically significant. HbA1c decreased in both groups, but in group I we obtained the best result. Leptin level after treatment was approximately the same in both groups. Also, blood pressure was reduced in both groups but results were similar.. Our study demonstrated that it is possible to break this metabolic vicious circle by raising testosterone levels in diabetic men with androgen deficiency. Re-instituting physiological levels of testosterone, as the study has shown, has an important role in reducing the prevalence of diabetic complications.

Topics: Adult; Aged; Blood Pressure; Diabetes Mellitus, Type 2; Hormone Replacement Therapy; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Testosterone

The present study was designed to determine the effect of different doses of the angiotensin II receptor blocker (ARB), candesartan, on circulating adiponectin and leptin levels as well as leptin adiponectin ratio (LAR) in hypertensive patients with multiple cardiovascular risk factors.Sixty-nine hypertensive patients were randomized to three groups: group 1 included patients treated with high doses of Candesartan (32 mg); group 2 included patients treated with conventional doses of Candesartan (16 mg); and group 3 included patients that received antihypertensive treatment other than ARBs or angiotensin-converting-enzyme inhibitors. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, c-reactive protein, aldosterone, renin, Homeostasis model assessment-insulin resistance, leptin, adiponectin and LAR. Baseline adiponectin, leptin, and LAR levels did not differ significantly between the three groups. After 6 months of treatment, LAR was significantly higher in group 3 than group 1 (P = .007) or group 2 (P = .023). Differences between effects of high (32 mg) and conventional doses (16 mg) of Candesartan on LAR were not observed (P = .678). Marginal across-group differences were detected for posttreatment circulating adiponectin level (P = .064). Univariate general linear model (GLM) analysis of posttreatment LAR detected significant by-group differences even after adjustment for age, gender, baseline values of LAR, and blood pressure. In this model, group was the only significant predictor of LAR after controlling for these variables. Treatment with high doses of the ARB, candesartan, is associated with significantly reduced LAR and marginally increased circulating adiponectin levels in hypertensive patients with multiple cardiovascular risk factors.

Topics: Adipokines; Adiponectin; Angiotensin Receptor Antagonists; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Cardiovascular Physiological Phenomena; Female; Homeostasis; Humans; Hypertension; Leptin; Male; Middle Aged; Renin-Angiotensin System; Tetrazoles

Some angiotensin receptor blockers (ARBs), including irbesartan, increase the peroxisome proliferator-activated receptor (PPAR)-g activity in vitro. The aim of this study was to evaluate the interactions between obesity and the effects of irbesartan on inflammatory cytokines in chronic glomerulonephritis patients without diabetes.. The anti-inflammatory effects of irbesartan were evaluated in 29 hypertensive chronic glomerulonephritis patients without diabetes in a prospective, single-arm study.. Following treatment with irbesartan for 26 weeks, blood pressure and proteinuria significantly decreased, as previously reported (blood pressure decreased from 142±1/87±1 to 131±1/81±1 mmHg and the urine protein/creatinine ratio decreased from 1030±143 to 779±121 mg/g Cr). BMI did not significantly change after the study. Among the inflammatory parameters, the concentrations of adiponectin and high-sensitivity C-reactive protein (hsCRP) significantly improved after treatment; however, the changes in the concentrations of interleukin-6 (IL-6), tumor necrosis factor (TNF)-a and leptin did not reach statistical significance. Moreover, the changes in these five parameters following treatment were moderately correlated with the BMI values obtained at the initiation of the study, and the improvements were particularly prominent in those with a BMI greater than 25. Improvements in proteinuria were significantly correlated with increases in the adiponectin concentration, but not with BMI. There was also a moderate correlation between the changes in the adiponectin and insulin concentrations.. Irbesartan improves metabolic parameters in nondiabetic hypertensive chronic glomerulonephritis patients, especially those with a high BMI. Improving the adiponectin concentration may be important for reducing proteinuria.

Topics: Adiponectin; Angiotensin II Type 1 Receptor Blockers; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Body Mass Index; C-Reactive Protein; Chronic Disease; Cytokines; Female; Glomerulonephritis; Humans; Hypertension; Inflammation Mediators; Interleukin-6; Irbesartan; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Proteinuria; Tetrazoles; Tumor Necrosis Factor-alpha

Obesity and arterial hypertension are tightly connected. Obese individuals show significant elevation of vasoconstrictory muscle sympathetic nerve activity (MSNA). Obesity-related hyperleptinemia might play a key role in mediating these effects. Leptin is synthesized in proportion to body fat mass and activates SNA in animal models. In humans, however, direct evidence linking hyperleptinemia to sympathetic activation has not yet been established. In the present study, we characterize the effects of acute hyperleptinemia on microneurographically recorded SNA in humans.. In a balanced, double-blind crossover design, 12 healthy normal-weight males received an iv bolus of leptin or placebo. MSNA (bursts per minute) was continuously recorded using a microneurographic technique. Ten-minute periods were analyzed at resting periods before (t-100) and at 20 (t20), 60 (t60), and 140 (t140) minutes after substance administration. Blood pressure and heart rate (HR) were recorded simultaneously.. Baseline values of MSNA, blood pressure, and HR were comparable in both conditions (MSNA: t-100, 24.3 ± 1.6 vs 22.7 ± 1.7, not significant). After application of leptin, MSNA showed a significant increase (t20, 31.0 ± 1.9 vs. 24.9 ± 1.8, P = .05) that persisted until the end of the experiment (t60, P = .008; t140, P = .004). There were no significant changes in blood pressure and HR.. Acute experimental hyperleptinemia has significant central nervous excitatory effects on vasoconstrictory sympathetic outflow as measured by MSNA in healthy men. These results suggest that leptin acts as an important mediator linking obesity to elevated MSNA and potentially to the development of hypertension.

Topics: Acute Disease; Adult; Blood Pressure; Cross-Over Studies; Double-Blind Method; Heart Rate; Humans; Hypertension; Injections, Intravenous; Leptin; Male; Muscle, Skeletal; Obesity; Pressoreceptors; Sympathetic Nervous System; Vasoconstriction; Young Adult

We sought to determine whether the antihypertensive drug nebivolol has beneficial effects on vascular markers of inflammation and oxidation in obese African-American patients with hypertension when exposed to exercise-induced stress. Forty-three obese, African-American subjects with hypertension were treated with nebivolol (5-10 mg/day) for 8 weeks. Before treatment the subjects underwent an exercise treadmill study to a level of eight metabolic equivalents. Circulating levels of soluble interleukin-6 (sIL-6), vascular cell adhesion molecule (VCAM-1), adiponectin and leptin were measured at pre-treadmill, and 1 min, 30 min, 60 min and 24 h after treadmill. After the 8-week treatment period, exercise treadmill study and the measurement of markers were repeated. Treatment with nebivolol reduced levels of sVCAM-1 at pre-exercise by 21% and at 1 and 30 min by 12.5 and 20%, respectively (P<0.005 from corresponding time point). In nebivolol-treated patients there was a reduction in sIL-6 levels by 20% and pre-exercise and at 1 and 60 min by 19.7 and 33.5%, respectively (P<0.005 from corresponding time point). Treatment with nebivolol increased levels of serum adiponectin by 28% (P=0.012) and decreased levels of leptin by 32% (P<0.005 from pre-treatment). Treatment with nebivolol improves markers of inflammation and obesity in a high-risk African-American population. Moreover, this effect is potentiated in response to exercise-induced stress. These results suggest that nebivolol differentially regulates markers of inflammation and obesity, thereby providing vascular protection.

Topics: Adiponectin; Antihypertensive Agents; Benzopyrans; Biomarkers; Black or African American; Blood Glucose; Cholesterol, HDL; Cholesterol, LDL; Ethanolamines; Exercise; Female; Humans; Hypertension; Inflammation; Interleukin-6; Leptin; Lipids; Male; Middle Aged; Nebivolol; Obesity; Stress, Physiological; Treatment Outcome; Vascular Cell Adhesion Molecule-1

The aim of the study was to evaluate the effect of quinapril on HOMA-IR, high sensitive C-reactive protein and leptin. Total 54 hypertensive and 24 control subjects were included in this study. Blood pressure, leptin, high sensitive C-reactive protein, and HOMA-IR were determined at baseline and after 3 months quinapril treatment. After treatment with quinapril HOMA-IR (p = 0.04), high sensitive C-reactive protein (p = 0.027), and leptin (p = 0.046) were decreased in hypertensive patients. Quinapril may be used as a therapy for improving blood pressure as well as the insulin resistant, hyperleptinemic, and low-grade inflammatory state in hypertension.

Topics: Adult; Aged; Antihypertensive Agents; Blood Pressure; C-Reactive Protein; Female; Homeostasis; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Male; Middle Aged; Quinapril; Tetrahydroisoquinolines; Treatment Outcome

We evaluated the effects of body weight (BW) loss on blood pressure (BP) in overweight non-obese patients with stage 1 hypertension. We enrolled 376 overweight (body mass index (BMI) >or=25 and <30 kg m(-2)) stage 1 hypertensive patients in this prospective 12-month trial. Each patient received tailored, low caloric dietary advice. After 6 months, patients with a BW reduction <5% were excluded. Body weight, BMI, BP, fasting plasma glucose (FPG), fasting plasma insulin (FPI), leptin (pL), renin and aldosterone levels were evaluated at baseline and after 6 and 12 months. In 222 patients who completed the study, a mean weight reduction of 8.1 kg reduced systolic blood pressure (SBP) by 4.2 mm Hg and diastolic blood pressure (DBP) by 3.3 mm Hg (P<0.05), which was accompanied by a significant decrease in FPI, pL and aldosterone levels (P<0.05). Larger SBP/DBP reductions were observed in 106 patients with normalized BMI (-5/-4.5 mm Hg, P<0.01) compared with the 116 patients who did not become normalized (-3.3/-1.6 mm Hg). The former also presented with greater decreases in FPG, FPI, pL, renin and aldosterone levels. Of the 106 patients who had normalized BMI, 52 also had normalized BP. Clinical and metabolic characteristics of these patients were similar to those of the 56 patients who did not have normalized BP. In overweight, mild hypertensive patients, weight loss was effective in reducing BP and in reversing some endocrinologic alterations associated with being overweight. Half of the patients who had normalized BMI also had normalized BP, which could indicate that these patients essentially did not have a form of hypertension but that these effects were instead secondary to being overweight.

Topics: Aged; Aldosterone; Blood Glucose; Blood Pressure; Body Mass Index; Diet, Reducing; Female; Humans; Hypertension; Insulin; Leptin; Male; Middle Aged; Overweight; Prospective Studies; Renin; Weight Loss

Metabolic syndrome, a constellation of metabolic risk factors for type 2 diabetes and cardiovascular disease, is one of the fastest growing disease entities in the world. Weight loss is thought to be a key to improving all aspects of metabolic syndrome. Research studies have suggested benefits from diets rich in vegetables and fruits in helping individuals reach and achieve healthy weights.. To evaluate the effects of a ready to serve vegetable juice as part of a calorie-appropriate Dietary Approaches to Stop Hypertension (DASH) diet in an ethnically diverse population of people with Metabolic Syndrome on weight loss and their ability to meet vegetable intake recommendations, and on their clinical characteristics of metabolic syndrome (waist circumference, triglycerides, HDL, fasting blood glucose and blood pressure).A secondary goal was to examine the impact of the vegetable juice on associated parameters, including leptin, vascular adhesion markers, and markers of the oxidative defense system and of oxidative stress.. A prospective 12 week, 3 group (0, 8, or 16 fluid ounces of low sodium vegetable juice) parallel arm randomized controlled trial. Participants were requested to limit their calorie intake to 1600 kcals for women and 1800 kcals for men and were educated on the DASH diet. A total of 81 (22 men & 59 women) participants with Metabolic Syndrome were enrolled into the study. Dietary nutrient and vegetable intake, weight, height, leptin, metabolic syndrome clinical characteristics and related markers of endothelial and cardiovascular health were measured at baseline, 6-, and 12-weeks.. There were significant group by time interactions when aggregating both groups consuming vegetable juice (8 or 16 fluid ounces daily). Those consuming juice lost more weight, consumed more Vitamin C, potassium, and dietary vegetables than individuals who were in the group that only received diet counseling (p < 0.05).. The incorporation of vegetable juice into the daily diet can be a simple and effective way to increase the number of daily vegetable servings. Data from this study also suggest the potential of using a low sodium vegetable juice in conjunction with a calorie restricted diet to aid in weight loss in overweight individuals with metabolic syndrome.

Topics: Adult; Aged; Beverages; Biomarkers; Blood Pressure; Counseling; Diet Records; Diet, Sodium-Restricted; Female; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Prospective Studies; Sodium, Dietary; Texas; Vegetables; Weight Loss

Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD). Several studies pointed out the possible role of increased leptin in NAFLD in humans. The aim of this study is to determine the effect of metformin on plasma leptin levels in obese patients with type 2 diabetes mellitus and NAFLD compared with lifestyle interventions. Thirty-four obese patients with newly diagnosed type 2 diabetes mellitus were prospectively followed for 6 months. All patients had ultrasonographic evidence of NAFLD at baseline. The patients were randomized into two groups: group 1 (n = 15) followed lifestyle changes only and group 2 (n = 19) received metformin (1,700 mg/day). At the end of treatment, BMI, WHR, HbA1c, fasting glucose, leptin, HOMA-IR, alanine aminotransferase values decreased in both groups. No significant difference in the end-points was observed between two groups. Only in group 2, LDL decreased and HDL increased significantly. Liver echogenity decreased significantly at the end of study in both groups. The percentage of patients who no longer had evidence of NAFLD was not significantly different between the groups (20% of patients on lifestyle intervention vs. 16% of patients on metformin). The data demonstrate that, metformin and lifestyle interventions equally affected the plasma leptin levels, BMI and degree of NAFLD in obese patients with type 2 diabetes mellitus. In addition, the effects of metformin on the variables were not found to be mediated by leptin.

Topics: Adult; Body Mass Index; Diabetes Mellitus, Type 2; Exercise; Fatty Liver; Female; Glycated Hemoglobin; Humans; Hypertension; Hypoglycemic Agents; Insulin; Insulin Resistance; Leptin; Life Style; Lipoproteins; Liver Function Tests; Male; Metformin; Middle Aged; Obesity; Triglycerides

Conjugated linoleic acid (CLA) refers to a group of positional and geometrical conjugated dienoic isomers of linoleic acid. Our aim was to investigate the effect of 8-week dietary CLA supplementation on blood pressure, concentrations of plasma adiponecin, leptin, and as well as angiotensin-converting enzyme (ACE) activity in obese hypertensive subjects.. Eighty obese individuals with stage 1 uncontrolled essential hypertension were randomized in a double-blind, placebo-controlled trial. Participants were randomized to a daily dose of 4.5 g/day CLA (nine 0.5-g capsules; a 50:50 isomer blend of c 9,t 11 and t 10,c 12 CLA) with 37.5 mg/day ramipril (group 1) or placebo with 37.5 mg/day ramipril (group 2) for 8 weeks. Baseline and endpoint systolic BP, diastolic BP, and concentrations of plasma adiponecin, leptin, angiotensinogen, and ACE activity were measured.. Treatment with CLA significantly enhanced the reduction effect of ramipril on systolic BP and diastolic BP (P < 0.05). It also increased plasma adiponectin concentration (P < 0.05) and decreased plasma concentrations of leptin and angiotensinogen (P < 0.05); however, significant change was not observed in ACE activity.. An 8-week long supplementation of CLA enhanced the effect of ramipril on blood pressure reduction in treated obese hypertensive patients. The antihypertensive effect of CLA might be related to the changed secretion of hypertensive adipocytokines in plasma.

Topics: Adiponectin; Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Blood Pressure; Dietary Supplements; Dose-Response Relationship, Drug; Double-Blind Method; Drug Synergism; Female; Follow-Up Studies; Humans; Hypertension; Leptin; Linoleic Acids, Conjugated; Male; Middle Aged; Obesity; Ramipril; Treatment Outcome

Insulin resistance, a key component of the metabolic syndrome, is a risk factor for diabetes mellitus and cardiovascular disease. Acetyl-L-carnitine infusion acutely ameliorated insulin sensitivity in type 2 diabetics with insulin resistance. In this sequential off-on-off pilot study, we prospectively evaluated the effects of 24-week oral acetyl-L-carnitine (1 g twice daily) therapy on the glucose disposal rate (GDR), assessed by hyperinsulinemic euglycemic clamps, and components of the metabolic syndrome in nondiabetic subjects at increased cardiovascular risk a priori segregated into 2 groups with GDR < or =7.9 (n=16) or >7.9 (n=16) mg/kg per minute, respectively. Baseline GDR and systolic blood pressure were negatively correlated (n=32; P=0.001; r=-0.545), and patients with GDR < or =7.9 mg/kg per minute had higher systolic/diastolic blood pressure than those with higher GDR. Acetyl-L-carnitine increased GDR from 4.89+/-1.47 to 6.72+/-3.12 mg/kg per minute (P=0.003, Bonferroni-adjusted) and improved glucose tolerance in patients with GDR < or =7.9 mg/kg per minute, whereas it had no effects in those with higher GDRs. Changes in GDR were significantly different between groups (P=0.017, ANCOVA). Systolic blood pressure decreased from 144.0+/-13.6 to 135.1+/-8.4 mm Hg and from 130.8+/-12.4 to 123.8+/-10.8 mm Hg in the lower and higher GDR groups, respectively (P<0.05 for both; P<0.001 overall) and progressively recovered toward baseline over 8 weeks posttreatment. Total and high molecular weight adiponectin levels followed specular trends. Diastolic blood pressure significantly decreased only in those with higher GDRs. Treatment was well tolerated in all of the patients. Acetyl-L-carnitine safely ameliorated arterial hypertension, insulin resistance, impaired glucose tolerance, and hypoadiponectinemia in subjects at increased cardiovascular risk. Whether these effects may translate into long-term cardioprotection is worth investigating.

Topics: Acetylcarnitine; Adiponectin; Administration, Oral; Adult; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Double-Blind Method; Drug Administration Schedule; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Prospective Studies; Treatment Outcome; Vitamin B Complex; Young Adult

Reciprocal relationships between endothelial dysfunction and insulin resistance imply that improvement in endothelial dysfunction will have beneficial metabolic consequences. We hypothesized that amlodipine therapy in hypertensive subjects will improve endothelial dysfunction and metabolic parameters.. Amlodipine (10 mg daily for 8 weeks) or placebo was given to each 45 patients with mild to moderate hypertension in a randomized, double-blind, placebo-controlled, and parallel study. Age, sex, and body mass index were matched.. Amlodipine therapy significantly reduced systolic and diastolic blood pressure and increased HDL-cholesterol to greater extent than placebo therapy (all P<0.001). Amlodipine therapy significantly improved flow-mediated dilator response to hyperemia and reduced plasma malondialdehyde levels to a greater extent than placebo (P<0.001 and P=0.035). Amlodipine therapy significantly increased plasma adiponectin levels (P=0.009) and decreased plasma leptin and resistin levels (P<0.001 and P=0.025, respectively) to a greater extent than placebo. Correlations were noted between percent changes in adiponectin levels and percent changes in HDL-cholesterol (r=0.348, P=0.019) and QUICKI (r=0.326, P=0.029) following amlodipine therapy. Only changes in HDL-cholesterol (beta=0.469, P=0.019) and QUICKI (beta=1.786, P=0.069) were independent predictors of changes in adiponectin levels (multivariate regression analysis). We also observed inverse correlations between percent changes in leptin levels and percent changes in QUICKI (r=-0.569, P<0.001) following amlodipine therapy with changes in QUICKI (beta=1.810, P<0.001) as an independent predictor of changes in leptin levels.. Amlodipine therapy improves blood pressure, endothelial function, and metabolic parameters in patients with hypertension.

Topics: Adiponectin; Amlodipine; Antihypertensive Agents; Biomarkers; Cholesterol, HDL; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hypertension; Leptin; Male; Malondialdehyde; Middle Aged; Placebos; Regression Analysis; Resistin; Statistics, Nonparametric; Treatment Outcome

To observe the effect of fish oil supplementation on arterial elasticity and blood pressure (BP) in overweight hypertensive patients.. This was a double-blind, randomized and placebo-controlled clinical study, in which 52 overweight hypertensive patients from a community were selected and randomly allocated to two groups (26 in the fish oil group (3 g day(-1), fish oil capsules) and 26 in the placebo group (only capsules). All the subjects were follow-up for 8 weeks. The arterial elasticity was determined by CVProfilor DO-2020 and expressed as elasticity indexes (C(1)-large artery and C(2)-small artery). During the follow-up, totally nine cases were dropped out (three cases from the fish oil group and six cases from the placebo group).. After 8 weeks follow-up, the large artery elasticity in the fish oil group, compared with its baseline, was significantly improved (C(1): 15.5+/-1.5 vs 12.8+/-3.7 ml mm Hg(-1) x 10), whereas no effects were found in the placebo group (C(1): 13.0+/-3.4 vs 13.4+/-3.8 ml mm Hg(-1) x 10), P=0.027, RM-ANOVA across the two groups. The small artery elasticity (C(2)), BP and pulse pressure were not found any changes, either in the fish oil group or in the placebo group. At same time, the serum soluble vascular cell adhesion molecule-1(sVCAM-1) and leptin levels, the lipid profile and insulin sensitivity index (ISI) as well, did not show significant differences between two groups.. Fish oil supplementation certainly would improve large arterial elasticity but no effect on BP in overweight hypertensive patients. Further study is needed to confirm the benefits of fish oil supplementation on age-related increases in arterial stiffness.

Topics: Adult; Arteries; Blood Pressure; Dietary Supplements; Double-Blind Method; Elasticity; Female; Fish Oils; Humans; Hypertension; Leptin; Male; Overweight; Solubility; Vascular Cell Adhesion Molecule-1

Adipokines are substances produced by the adipose tissue that may play significant roles in the mechanisms contributing to the development of atherosclerosis. Thiazolidinediones have been shown to improve endothelium-dependent vasodilation and to exert multiple antiatherosclerotic effects. This study tested the hypotheses that nondiabetic patients with cardiovascular risk factors have altered levels of adipokines that can be modified by pioglitazone treatment. Eighty patients with hypertension or hypercholesterolemia were in a double-blinded, placebo-controlled, crossover study. In each treatment phase, patients received pioglitazone 45 mg/day or placebo for 8 weeks. Endothelial function studies and biochemical assays were performed at the end of each 8-week treatment period. Twenty-two normal volunteers, matched with patients for age, gender, and body mass index, were recruited as a control group. Compared with controls, placebo-treated patients had lower adiponectin levels (11,160 +/- 763 vs 6,078 +/- 385 ng/ml, p <0.001) and similar plasma leptin levels (21.5 +/- 3.8 vs 16.2 +/- 1.5 ng/ml, p = 0.128) and resistin levels (5.1 +/- 0.4 vs 4.4 +/- 0.2 ng/ml, p = 0.250). In patients, pioglitazone treatment markedly increased adiponectin (+121%, p <0.001) and decreased resistin (-10.5%, p = 0.03). Leptin was not significantly decreased (-7.1%, p = 0.10). In multivariate analysis, pioglitazone-induced changes in endothelial reactivity to acetylcholine were the only significant predictor of increases in adiponectin. In conclusion, in nondiabetic patients with major cardiovascular risk factors, pioglitazone treatment beneficially influences circulating adipokine levels. The relation between the increase in adiponectin levels and the improvement in endothelial vasodilator activity suggests a mechanistic link between vascular effects and adiponectinemia.

Topics: Adipokines; Adiponectin; Adult; Aged; Case-Control Studies; Cross-Over Studies; Double-Blind Method; Endothelium, Vascular; Female; Humans; Hypercholesterolemia; Hypertension; Hypoglycemic Agents; Leptin; Male; Middle Aged; Pioglitazone; PPAR gamma; Resistin; Thiazolidinediones; Treatment Outcome

Telmisartan, a new angiotensin II type 1 receptor blocker (ARB), was recently reported to stimulate PPARgamma, and stronger effects of Telmisartan on insulin sensitivity has been expected than the class effect of ARB. In the present study, we examined the effects of Telmisartan on insulin sensitivity and adipokine levels in hypertensive and type 2 diabetic patients. Outpatients with both hypertension and type 2 diabetes mellitus (n=36; male 23, female 13), received 20-40mg Telmisartan orally once daily for 6 months. Physical examinations and blood or urine tests were performed before and 3 or 6 months after starting Telmisartan treatment. Results were statistically compared using Wilcoxon analysis. Telmisartan treatment for 3 or 6 months reduced systolic and diastolic blood pressure and urinary albumin excretion. Fasting plasma glucose, HbA1c, total and HDL-cholesterol, triglyceride, body weight, BMI and waist length were not changed. Fasting IRI and HOMA-IR were significantly decreased after Telmisartan treatment, suggesting the improved insulin sensitivity. Total and high molecular adiponectin were not changed. Interestingly, serum leptin was significantly increased by 3 months Telmisartan treatment, suggesting a possible involvement of leptin in improved insulin sensitivity. In conclusion, Telmisartan improved insulin resistance with increased serum leptin level in hypertensive and type 2 diabetic patients.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Albuminuria; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Benzoates; Blood Pressure; Body Mass Index; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diet, Diabetic; Female; Humans; Hypertension; Hypoglycemic Agents; Leptin; Lipids; Male; Middle Aged; Telmisartan

Topics: Adiponectin; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Cholesterol, HDL; Dihydropyridines; Endothelium, Vascular; Humans; Hypertension; Leptin; Nitrophenols; Organophosphorus Compounds; Placebos; Vasodilation

We examined the effects of a short-term low-calorie diet on the activity of the autonomic nervous system during stress tests in obese patients with hypertension by analysis of heart rate and blood pressure variability. Eighteen obese inpatients with essential hypertension were given a regular-calorie diet (1,600 kcal, NaCl 7 g) for 4 days, and then a low-calorie diet (1,100 kcal, NaCl 7 g) for 11 days. During both the regular-calorie diet and low-calorie diet, power spectral analysis of heart rate and blood pressure variability at rest and during mental arithmetic test, deep breathing test, isometric handgrip test or cold pressor test was performed. Body weight and 24-h ambulatory blood pressure were significantly lower during the low-calorie diet than during the regular-calorie diet. Systolic and diastolic blood pressure significantly increased over the handgrip test and cold pressor test during both diets. The low frequency component (LF) of systolic blood pressure, a marker of sympathetic activity to the vasculature, during the deep breathing test and cold pressor test were significantly lower on the low-calorie diet than the regular-calorie diet. The blood leptin concentration was also significantly lower on the low-calorie diet than the regular-calorie diet. The decrease in body weight was positively correlated with the decrease in blood leptin concentration. The LF/high frequency component (HF) ratio of the RR interval at rest on the regular-calorie diet was negatively correlated with the decrease in blood leptin concentration. These results suggest that the autonomic nervous function assessed by analysis of heart rate and blood pressure variability during stress tests may be improved by weight loss due to a short-term low-calorie diet in obese patients with hypertension.

Topics: Blood Pressure; Body Weight; Caloric Restriction; Diet, Reducing; Exercise Test; Female; Heart Rate; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Sympathetic Nervous System; Vagus Nerve

Obesity-induced hypertension and essential hypertension in lean patients are two different forms of hypertension. The main goal of this study was to test whether there are differences in biochemical parameters between subjects with obesity-associated hypertension and those with essential hypertension. We examined whether the biochemical responses to angiotensin-converting enzyme inhibitor (ACEI) ramipril therapy reveal properties of these two conditions that might explain the differences in clinical outcome. Before ramipril therapy, the hypertensive group exhibited increases in ACE activity (p<0.05), plasma malondialdehyde (MDA) concentration and the malondialdehyde/nitric oxide end-product ratio (MDA/NO(x)) (p<0.05), and decreases in xanthine oxidase (XO) activity (p<0.05) and plasma nitric oxide end-product (NO(x)) level (p<0.01). Before medication, plasma endothelin-1 (ET-1), plasma leptin, and leptin receptor levels were normal. Following ramipril treatment, ACE activity normalized. Before ACE inhibitor treatment, the obese-hypertensive group exhibited elevated levels of plasma ET-1 (p<0.05), plasma leptin (p<0.01), XO activity (p<0.05), plasma MDA and MDA/NO(x) (p<0.05), and reduced levels of plasma NO(x)(p<0.01) and leptin receptors (p<0.001). Following medication, the plasma NO(x) level, MDA/NO(x), and XO activity returned to normal while ACE activity decreased (p<0.001). In patients with essential hypertension, NO availability and ACE activity, and in those with obesity-associated hypertension, hyperleptinemic effects, NO level, endothelin-1 concentration and XO activity, may be important factors in the pathology.

Topics: Adolescent; Angiotensin-Converting Enzyme Inhibitors; Body Mass Index; Endothelin-1; Female; Humans; Hypertension; Leptin; Male; Malondialdehyde; Nitric Oxide; Obesity; Peptidyl-Dipeptidase A; Ramipril; Xanthine Oxidase

Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine with potential atherogenic properties whose role in human obesity has been recently suggested. The aim of our study was to analyze the physiologic distribution of IL-18 among sexes and all decades of the adult life in a healthy population randomly selected and to study its relationship with anthropometric, body composition measurements and leptin concentrations. We also studied the relationship of IL-18 with smoking and arterial hypertension, known risk factors implicated in atherogenesis.. One hundred and thirty four men and 127 healthy women were included in the study. Plasma concentrations of IL-18 and leptin were determined in all subjects. Body composition was evaluated by bioelectrical impedanciometry.. IL-18 was distributed similarly in men and women and throughout decades. No significant differences were found in IL-18 between obese and normal-weight men and women according to their body mass index and body fat content. Higher IL-18 concentrations were found in subjects with arterial hypertension. In the bivariate correlation analysis only waist to hip ratio correlated weakly with IL-18 in the whole population (r=0.12, p=0.04). In the multiple regression analysis the relationship between IL-18 and waist to hip ratio lost significance after adjusting for age, sex and body mass index. However, IL-18 remained associated with arterial hypertension (adjusted r2=0.25, p=0.023).. The lack of correlation between IL-18 with anthropometric, body composition variables and leptin in our healthy population argues against a role of this cytokine in obesity. Moreover, our findings suggest the implication of this interleukin in the atherogenic process induced by arterial hypertension.

Topics: Adolescent; Adult; Aged; Anthropometry; Body Composition; Body Mass Index; Female; Humans; Hypertension; Interleukin-18; Leptin; Male; Middle Aged; Waist-Hip Ratio

Obesity is often complicated by hypertension, and both conditions are risk factors for atherosclerosis. Leptin has attracted attention as a possible cause of hypertension in obese persons. We investigated the effect of a slow-release alpha1-receptor blocker, bunazosin hydrochloride, on leptin levels and insulin resistance in obese hypertensive patients with hyperleptinemia. The subjects were 17 patients (12 men and 5 women aged 56.1 +/- 12.2 years) with essential hypertension who were not receiving alpha1-receptor blockers. They had a body mass index (BMI) > or = 25 kg/m2 and a plasma leptin concentration > or = 5 ng/ml. They received oral therapy with bunazosin hydrochloride at doses of up to 9 mg/day. The plasma leptin concentration, body weight, blood pressure, heart rate, fasting blood glucose, plasma insulin concentration, and free fatty acid level were compared between before and after treatment. Although there was no significant change of BMI, there was a significant decrease of plasma leptin after treatment (10.6 +/- 5.4 ng/ml vs. 8.7 +/- 3.4 ng/ml, p = 0.0128), as well as a significant decrease of plasma insulin (9.8 +/- 4.8 microU/ml vs. 8.1 +/- 4.6 microU/ml, p = 0.0494) and HOMA-R (2.9 +/- 2.1 vs. 2.2 +/- 1.5, p = 0.0237). In conclusion, bunazosin hydrochloride reduced the plasma leptin level and improved insulin resistance in hypertensive patients with obesity and hyperleptinemia.

Topics: Adrenergic alpha-1 Receptor Antagonists; Adrenergic alpha-Antagonists; Adult; Aged; Blood Pressure; Body Mass Index; Delayed-Action Preparations; Fatty Acids, Nonesterified; Female; Heart Rate; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Quinazolines; Receptors, Leptin; Treatment Outcome

The objective of this study is to assess the effects of sibutramine on body weight, body fat distribution, insulin resistance, plasma leptin, lipid profile and blood pressure profiles in hypertensive obese patients.. Eighty-six central obese hypertensive patients (BMI = 39 +/- 5 kg/m(2), 84% of women, 48 +/- 8.5 years old) were placed on a hypocaloric diet and placebo therapy for 4 weeks. They were then randomized to receive sibutramine (10 mg) or placebo for 24 weeks. Both, before therapy and at the end of the study, the waist and hip circumferences were measured and the waist/hip ratio (WHR) was calculated; abdominal ultrasonography was performed in order to estimate the amount of subcutaneous fat (SF) and visceral fat (VF), and the visceral/subcutaneous ratio. Beyond HOMA-r, another insulin resistance index (IRIp) was calculated by means of the formula: peak of blood glucose after oral glucose load x plasma insulin level/10(4). Fasting plasma leptin and lipid levels were also determined.. Sibutramine induced greater weight reduction than placebo (6.7 vs. 2.5%, p < 0.001). Reductions in WHR (0.97 +/- 0.08 vs. 0.94 +/- 0.07, p < 0.01), IRIp (0.11 +/- 0.07 vs. 0.09 +/- 0.06 mmol mu/l(2)) and VF (6.4 +/- 2.4-6.0 +/- 2.4 cm, p < 0.01) were observed only with sibutramine. Plasma leptin decreased with placebo (24 +/- 15 vs. 18 +/- 10 UI/l, p < 0.01), but not with sibutramine (18.8 +/- 8.4 vs. 18.2 +/- 13.2 UI/l). No clinically significant change in lipid profile was observed in both groups. Moreover, office and 24-h blood pressure values did not change during placebo or sibutramine therapy, whereas a significant increase in office heart rate, from 78.3 +/- 7.3-82 +/- 7.9 b.p.m., p = 0.02, was observed with sibutramine.. Sibutramine therapy induced greater body weight loss than placebo in hypertensive obese patients. This was associated with WHR reduction, decreases in VF and insulin resistance. The maintenance of leptin levels during sibutramine therapy may be important to avoid weight recovery, although this finding must be confirmed by other prospective studies.

Topics: Adult; Antihypertensive Agents; Appetite Depressants; Chi-Square Distribution; Cyclobutanes; Drug Therapy, Combination; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin Resistance; Leptin; Lipids; Male; Middle Aged; Obesity; Waist-Hip Ratio; Weight Loss

Aim of this study was to compare the effect of valsartan and felodipine on blood pressure (BP), plasma leptin (L), insulin sensitivity and plasma norepinephrine (NE) in obese hypertensive patients. Ninty-six obese patients (body mass index [BMI] > or = 30 kg/m2) with mild to moderate essential hypertension (diastolic blood pressure [DBP] > 90 and < 110 mmHg, as evaluated with an appropriately sized cuff) aged 31-60 years, were randomized to a valsartan (80 mg/day for 16 weeks; n = 48) or felodipine (5 mg/day for 16 weeks; n = 48) treatment group after a 2-week wash-out period. After the first 4 weeks of treatment there was a titration with dose-doubling in non responder patients (DBP > 90 mmHg). At the end of the placebo period and of active treatment period, BP and BMI were evaluated and a venous sample was drawn at the same hour in the morning to evaluate plasma L and NE. Insulin resistance index (HOMA-IR) was calculated. No dietary advice was prescribed. Both valsartan and felodipine significantly decreased BP values (-19.3/15 mmHg and -18.9/13.6 mmHg, respectively p < 0.001 vs. placebo), with no difference between treatments. However, felodipine increased plasma NE (+124 pg/ml, +38.2%, p < 0.05 vs. placebo and < 0.01 vs. valsartan) and had no effect on L, body weight and HOMA-IR index, while valsartan did not modify NE and produced a significant reduction in L (-3.7 ng/ml, -10.1%, p < 0.05 vs. placebo), BMI (-1.7 kg/m2, -4.7%, p < 0.01 vs. placebo) and HOMA-IR index (-1.6, -20%, p < 0.05 vs. placebo). These results suggest that in hypertensive obese subjects, treatment with valsartan might offer an advantage over treatment with felodipine, since valsartan may help to improve obesity-related disorders in addition to lowering BP.

Topics: Aged; Antihypertensive Agents; Felodipine; Female; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Tetrazoles; Treatment Outcome; Valine; Valsartan

In rats leptin increases sympathetic activity, and an inhibitory effect on leptin synthesis and release has been demonstrated for the catecholamines, both in adipocyte cell cultures and in healthy experimental animals. The aim of this study was to evaluate the relationship between leptin and heart sympathetic activity as well as changes in leptin levels after the administration of drugs that modify sympathetic activity.. We performed a randomized, blinded, before-after trial in 81 normotensive obese and non-obese subjects. They were studied before and after treatment with enalapril (5 mg every 12 hours) or clonidine (0.1 mg every 12 hours) for 7 days.. Obese subjects had higher values for percent body fat (p < 0.0005), triglycerides (p < 0.05), leptin (p < 0.0005), and low frequency/high frequency ratio at night (LF/HFn, p = 0.05). After enalapril or clonidine treatment, leptin levels were not modified. Both drugs significantly diminished the systolic and diastolic blood pressures. In the obese group, clonidine and enalapril diminished the LF/HFn ratio (p < 0.05). The LF/HF index showed a univariate correlation with body mass index, leptin, systolic blood pressure, insulin, age and triglyceride levels. In the multiple regression analysis for factors associated with the LF/HF ratio, only leptin, age and insulin were included in the model. The r2 of the model was 0.3 (p = 0.0003).. A higher level of heart sympathetic activity is found in normotensive obese as compared with non-obese subjects. Both clonidine and enalapril reduced heart sympathetic activity in obese subjects without a change in fasting leptin levels.

Topics: Adipose Tissue; Adrenergic alpha-Agonists; Adult; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Biomarkers; Blood Pressure; Body Mass Index; Clonidine; Diastole; Enalapril; Female; Heart Rate; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Statistics as Topic; Systole; Treatment Outcome

Leptin, a circulating hormone secreted from adipocytes, is an index of adiposity and is reduced by caloric restriction and weight loss. A recent population study suggested that dietary-derived omega3 fatty acids lower leptin levels independent of body fat.. To examine whether dietary fish enhanced the effects of weight loss on serum leptin levels, in 69 overweight, treated hypertensive men and women.. Participants were randomized to a daily fish meal, a weight-reduction regimen, the two regimens combined or a control group for 16 weeks.. A total of 63 individuals completed the study. Weight fell 5.6 +/- 0.8 kg with energy-restriction. Blood pressure (BP) reductions in the combined fish-weight loss group were twice that seen with either intervention alone. At baseline, in all groups combined, serum leptin levels correlated with serum insulin (r = 0.307, P = 0.014), but not with body weight. The greatest change in serum leptin occurred in the fish-weight loss group (control, 0.60 +/- 0.76 ng/ml; fish, 1.20 +/- 0.79 ng/ml; weight loss, -1.40 +/- 1.05 ng/ml; fish-weight loss, -5.08 +/- 1.64 ng/ml). In the fish-weight loss group, the change in serum leptin was predicted by changes in serum insulin (r = 0.488, P = 0.038), 24-h BP (systolic BP (SBP): r = 0.435, P = 0.060; diastolic BP (DBP): r = 0.563, P = 0.018) and 24-h heart rate (0.584, P = 0.028). Using general linear models, there was a significant fish x weight-loss interaction (P = 0.008) on post-intervention serum leptin after adjustment for baseline levels, independent of post-intervention insulin.. A daily fish meal as part of a weight-reducing regimen was more effective than either measure alone at reducing leptin levels. Reductions in leptin may be related to the substantial fall in BP seen with the fish-weight loss program.

Topics: Animals; Blood Glucose; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Body Weight; Diet; Diet, Reducing; Energy Intake; Fatty Acids; Female; Fishes; Heart Rate; Humans; Hypertension; Insulin; Leptin; Lipids; Male; Middle Aged; Obesity; Phospholipids; Weight Loss

Results from animal experimentation suggest a 2-way interaction between leptin and the sympathetic nervous system, with leptin causing sympathetic activation and conversely, with the sympathetic system exercising regulatory feedback inhibition over leptin release. We have now tested this hypothesis in humans. In the absence of results from leptin infusions, to test for sympathetic stimulation of leptin release, we sought a quantitative naturalistic linkage of sympathetic activity with leptin plasma concentration across a broad range of leptin values in men of widely differing adiposity. Renal norepinephrine spillover was correlated with plasma leptin (r=0.628, P<0.01), but other measures of sympathoadrenal function did not. To test for sympathetic and adrenomedullary inhibition of leptin release, we studied clinical models of high sympathetic tone, heart failure, and essential hypertension, in which lowered plasma leptin levels might have been expected but were not found; a model of low sympathetic activity, pure autonomic failure, in which plasma leptin level was normal (6.1+/-1.2 vs 12.8+/-3.1 ng/mL in healthy subjects); and a clinical model of reduced epinephrine secretion, healthy aging, in which plasma leptin level again was normal (5.7+/-1.1 ng/mL vs 4.0+/-0.9 ng/mL in men >60 years and <35 years, respectively). Paradoxically, leptin concentration was elevated in heart failure, caused entirely by reduced renal clearance of leptin release, 142.0+/-30.5 mL/min, compared with 56.9+/-18.9 mL/min (P<0.05). These results provide some support for the view that leptin stimulates the sympathetic nervous system, at least for renal sympathetic outflow, but do not confirm the concept of regulatory feedback inhibition of leptin release by the sympathetic nervous system.

Topics: Adult; Aging; Antihypertensive Agents; Autonomic Nervous System Diseases; Clonidine; Epinephrine; Female; Humans; Hypertension; Infusions, Intravenous; Leptin; Male; Middle Aged; Nitroprusside; Norepinephrine; Obesity; Sympathetic Nervous System; Ventricular Dysfunction, Left

The aim of this study was to clarify the relation among systolic blood pressure (SBP), serum insulin, leptin, visceral fat accumulation and family history of hypertension, and to elucidate the pathophysiologic mechanism of blood pressure elevation in obese children. This study examined 109 obese children with a family history of hypertension (OF: 77 boys and 32 girls), and 83 obese children without such a history (ON: 60 boys and 23 girls). Body height and weight, and percent of body fat were measured and the percent of relative weight was calculated. Both boys and girls, the two groups were matched with respect to age, height, and weight. SBP was measured in the seated position using an automated recorder. Abdominal fat thickness (maximum preperitoneal fat thickness: Pmax; minimum subcutaneous fat thickness: Smin) were measured using ultrasonography. The fasting serum levels of insulin and leptin were measured by radioimmunoassay. All subjects were simply obese, without diabetic states. In both OF and ON, SBP was associated with insulin levels, leptin levels, and Pmax by simple regression analysis, and with insulin levels by stepwise regression analysis. Insulin levels were associated with leptin levels and Pmax by simple regression analysis, and with leptin levels by stepwise regression analysis. These findings indicated that SBP was associated with hyperinsulinemia, hyperleptinemia and visceral accumulation regardless of a family history of hypertension in obese children, as well as later in adult obesity. For primary prevention of hypertension, these results support the importance of implementation of a strategy to prevent obesity, especially visceral obesity. An effective strategy for preventing childhood obesity will contribute to a future decrement in cases of metabolic syndrome, including adulthood hypertension.

Topics: Adipose Tissue; Adolescent; Blood Pressure; Body Height; Body Weight; Child; Female; Humans; Hypertension; Insulin; Leptin; Male; Obesity; Regression Analysis

Hypertension is a complex trait with an ill-defined genetic predisposition, in which adrenergic mechanisms seem to be involved even at the early stages. Chromogranin A is a pro-hormone stored and released with catecholamines by exocytosis; its fragment catestatin, formed in vivo, inhibits further catecholamine release as an antagonist at the physiologic trigger for secretion, the neuronal nicotinic cholinergic receptor.. We measured catestatin by radioimmunoassay in n = 277 subjects stratified by blood pressure (n = 61 hypertensive, n = 216 normotensive), and if normotensive by genetic risk of developing hypertension: family history positive (n = 176) versus negative (n = 40). Maximum likelihood analysis tested for bimodality. Involvement of catestatin in pathophysiology was probed by measurements of catecholamines and leptin, and the hemodynamic responses to environmental (cold) stress.. The normotensive offspring of patients with hypertension already had diminished catestatin (P = 0.024), and family history was a better predictor of catestatin than age, ethnicity or gender (P = 0.014). Greater catestatin variance among family history-positive individuals (P = 0.021) suggested heterogeneity in this group, and a bimodal distribution (P < 0.001) identified 4.3% of individuals in a lower mode of catestatin values, all with positive family histories (P = 0.05). Catestatin correlated inversely with body mass index (r = -0.215, r(2) = 0.046, n = 276, P < 0.001) and plasma leptin (r = -0.203, r(2) = 0.041, n = 212, P = 0.003), while body mass index and leptin correlated directly (r = 0.59, r(2) = 0.350, n = 212, P < 0.001). Family history-positive individuals had greater epinephrine excretion (P = 0.037) in addition to diminished catestatin, suggesting an inhibitory effect of catestatin on chromaffin cells in vivo. Low plasma catestatin predicted enhanced pressor response to a sympathoadrenal stressor (cold stress; r = -0.184, r(2) = 0.034, n = 211, P = 0.007), suggesting an adrenergic mechanism whereby diminished catestatin might predispose to later development of hypertension. In white subjects, diminished catestatin also predicted greater systemic vascular resistance responses to cold stress (r = -0.307, r(2) = 0.094, n = 75, P = 0.007), a relationship not found in Blacks (r = 0.122, r(2) = 0.015, n = 94, P = 0.243).. We conclude that catestatin is diminished early in the course of development of hypertension, even in the normotensive offspring of patients with the disease. Low catestatin predicts augmented adrenergic pressor responses, suggesting a mechanism whereby diminished catestatin might increase the risk for later development of hypertension.

Topics: Adult; California; Catecholamines; Chromogranin A; Chromogranins; Cold Temperature; Female; Genetic Markers; Genetic Predisposition to Disease; Hemodynamics; Humans; Hypertension; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Peptide Fragments; Predictive Value of Tests; Statistics as Topic; Stress, Physiological; Time Factors

In humans, the kidney is involved in leptin clearance from the body. The present study was performed to assess the renal extraction of leptin in hypertensive patients with or without renal artery stenosis. Sixty-five hypertensive subjects (39 males and 26 females) underwent catheterization of the renal artery and both renal veins with blood sampling for measuring leptin levels. Blood flow to both kidneys was measured by the xenon washout technique. From these data, renal leptin uptake and renal fractional extraction of leptin were calculated. Endogenous creatinine clearance ranged from 24 to 191 ml/min in the males and from 20 to 149 ml/min in the females. In 25 patients, radiological signs of renal artery stenosis were present. Total renal leptin uptake by both kidneys averaged 141 +/- 47 ng x min(-1) x 100 g(-1). No differences in leptin uptake were found between males and females or between patients with or without renal artery stenosis. The average renal extraction fraction of leptin was 6 +/- 2%. Renal leptin uptake and renal extraction fraction of leptin did not correlate with arterial leptin concentrations or with blood pressure, endogenous creatinine clearance, or the presence or absence of renal artery stenosis. In hypertensive patients with or without renal artery stenosis, the kidney removes only a small fraction of circulating leptin from the body within one passage. This fraction remains relatively constant despite wide variations in renal function or circulating leptin.

Topics: Adolescent; Adult; Blood Pressure; Catheterization; Creatinine; Female; Humans; Hypertension; Kidney Function Tests; Leptin; Male; Middle Aged; Multivariate Analysis; Radiography; Renal Artery; Renal Artery Obstruction; Renal Circulation; Renal Veins; Sex Factors; Xenon

We performed this study to investigate whether changes in plasma glucose, insulin, and norepinephrine concentrations during an oral glucose tolerance test (OGTT) are associated with changes in plasma leptin levels in normotensive and hypertensive obese women. Plasma insulin, glucose, norepinephrine, and leptin concentrations were evaluated at the baseline and during OGTT in normotensive women (NT-Ob, N = 24, mean age 38.3+/-1.8 years, body mass index [BMI] 37.9+/-1.1 kg/m2) and hypertensive (HT-Ob, N = 25, mean age 37.7+/-1.9 years, BMI 39.4+/-1.3 kg/m2) obese women, and in a group of normal-weight women (controls, N = 20, mean age 38.3+/-1.3 years, BMI 23.1+/-0.4 kg/m2). The OGTT caused a significant increase in plasma leptin concentrations in both NT-Ob and HT-Ob groups, whereas no such change was detectable in control subjects. Area under curve (AUC) for plasma leptin showed a direct correlation with norepinephrine AUC in both NT-Ob (r = 0.73, P = .001) and HT-Ob (r = 0.74, P = .001) group, which was still detectable in multivariate analysis (P = .014 and P = .017, respectively). Our study confirms that glucose loading increases circulating leptin concentrations in obese women, and demonstrates the existance of an association between leptin and norepinephrine changes during OGTT in both normotensive and hypertensive obese women. We hypothesize that this association may reflect the lack of leptin suppression by catecholamines or a direct leptin-induced sympathoactivation. These findings suggest that leptin could be relevant in the regulation of blood pressure in obese women.

Topics: Adult; Blood Glucose; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Leptin; Norepinephrine; Obesity

Recent evidence shows that leptin may contribute to elevated blood pressure (BP) and interact with the renin-angiotensin-aldosterone and cellular immune systems. Altered T-cell activities and changes in T-cell subset ratios have also been reported in hypertension. However, little is known about the effects of AT1-receptor antagonism on T-cell activities and plasma leptin concentrations in primary hypertension. We have, therefore, investigated the relationship between leptin and T-cell activities and the effect of an AT1-receptor antagonist, losartan, in primary hypertension. Twenty recently-diagnosed and untreated young adults (11 males and 9 females, age; 39.9+/-7.6 years, range 23-49 years, BMI; 27.6+/-3.7kg/m2) and 20 normotensive healthy, age-, sex- and BMI-matched controls were studied. The [3H]-thymidine uptakes of cultured lymphocytes were determined, both spontaneously and after stimulation with phytohaemagglutinin. The tests were performed before and after three months of treatment with losartan. The results indicate that the blastogenic responses of T-cells to phytohaemagglutinin are significantly higher in the patient group compared with controls (p=0.02). After normalisation of BP, T-cell responses were significantly reduced and were lower than in the controls (p=0.01). Pretreatment plasma leptin levels were significantly higher in hypertensives than in controls (p=0.01). However, losartan treatment had no significant effect on leptin concentrations; moreover, no correlation between leptin levels and T-cell activity was found. Our data show that plasma leptin levels and T-cell activity are markedly enhanced in untreated essential hypertension and that the alteration of T-cell activity is not related to plasma leptin levels. Antihypertensive treatment with losartan decreases T-cell activities but does not influence plasma leptin levels. We conclude that leptin levels are not affected by AT1-receptor blockade and are not related to T-cell activity.

Topics: Adult; Antihypertensive Agents; Female; Humans; Hypertension; Leptin; Losartan; Male; Middle Aged; T-Lymphocytes

The effects of celiprolol on fasting plasma leptin levels, glucose tolerance, and insulin sensitivity were studied in a randomized, investigator-masked, and parallel clinical trial. Modified oral glucose tolerance tests (OGTT) were performed during the previous antihypertensive monotherapy (beta- or Ca-blocker, or ACE inhibitor), and 6 and 12 months after randomization to celiprolol (200-400 mg daily) or to control group, where the therapy was kept unchanged. One hundred sixty-nine dyslipidemic and hypertensive nondiabetics with an age range of 42-65 years and an average body mass index of 28.4 kg/m2 completed the study according to the protocol. The mean circulating leptin level decreased from 7.5 to 6.6 ng/mL in men (p < 0.05) and from 23.0 to 19.7 ng/mL in women during the 12-month celiprolol treatment. The incremental glucose area under the curve (AUC) in the 2-hour OGTT decreased from 3.8 to 3.0 h* mmol/L (p < 0.01), and insulin AUC decreased from 134 to 99 h* mU/L (p < 0.01). The insulin sensitivity index increased by 22% (p < 0.01) and the serum triglyceride level decreased by 15% in the celiprolol group. Changes in serum cholesterol were clinically insignificant. In the control group, no significant change was seen in any measured variable. A decrease in leptin levels in the celiprolol group was associated with improved insulin sensitivity, while the weight of the moderately obese patients did not change. The clinical significance of a 14% decrease in fasting plasma leptin level remains to be elucidated. The results suggest amelioration of leptin resistance during long-term celiprolol therapy.

Topics: Adrenergic beta-Antagonists; Celiprolol; Fasting; Female; Glucose Tolerance Test; Humans; Hyperlipidemias; Hypertension; Insulin; Leptin; Male; Middle Aged; Obesity; Patient Compliance

Leptin is a product of the ob gene and is secreted by the adipose tissue. It takes part in regulation of nervous, cardiovascular, endocrine system and renal functions. The aim of this study was to assess the influence of short term moderate exercise on serum leptin levels in patients with arterial hypertension. The study group consisted of 34 patients with essential hypertension: 15 women (48.9 +/- 12.1 years old) and 19 men (43.5 +/- 14.6 years old). There were 7 patients with stage I of hypertension, 17 patients with stage II of hypertension and 10 patients with stage III of hypertension. The blood samples were taken before and after the exercise test. Serum leptin levels were assessed by radioimmunoassay. Serum leptin levels were significantly higher in women then in men. The logarithm of serum leptin levels after the exercise was significantly lower than before (0.8 +/- 0.4 and 0.9 +/- 0.5 respectively). The moderate, short term exercise decreases serum leptin levels in the hypertensive patients.

Topics: Adipose Tissue; Adult; Aged; Body Mass Index; Female; Heart Rate; Humans; Hypertension; Leptin; Male; Middle Aged; Physical Exertion; Sex Factors

To test the hypothesis that hemodynamic measurements in patients with essential hypertension are related independently to plasma leptin levels.. We measured plasma leptin, insulin, office and ambulatory blood pressure and heart rate in 60 men with untreated mild hypertension.. Plasma leptin correlated significantly with body mass index (r = 0.43, P = 0.001), 24 h heart rate (r = 0.35, P = 0.006) and 24 h diastolic blood pressure (r = 0.27, P = 0.04) but not with age (r = 0.03; P = 0.85) or 24 h systolic blood pressure (r = -0.08, P = 0.56). Plasma leptin levels adjusted for body mass index correlated significantly with 24 h heart rate (r = 0.36, P = 0.005) but not with 24 h diastolic blood pressure (r = 0.19, P = 0.15). We divided the patient population into tertiles of body mass index-adjusted plasma leptin levels. Age, plasma insulin, blood pressure, smoking status and physical activity habits were similar across the adjusted leptin tertiles. Patients from the third tertile of adjusted plasma leptin distribution (those with leptin levels higher than would be expected on the basis of body mass index) had significantly faster ambulatory heart rates than subjects from both the first and the second tertiles. The difference in heart rate across the three tertiles was most pronounced for the night-time values.. In patients with essential hypertension, heart rate is faster in those patients with higher plasma leptin levels. This relationship is independent of age, body mass index, insulin levels, blood pressure level, smoking status and physical activity.

Topics: Adipose Tissue; Adult; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Body Mass Index; Circadian Rhythm; Heart Rate; Humans; Hypertension; Leptin; Life Style; Male; Prognosis; Proteins; Radioimmunoassay

Leptin is produced and released by adipocytes in proportion to fat stores. Leptin as an anorectic hormone plays an important role in the regulation of food intake, energy expenditure, and insulin secretion. In contrast, neuropeptide Y, insulin, cortisol, and growth hormone are presumed to be appetite modulators. Leptin and neuropeptide Y are both involved in the activation of sympathetic tone. Increased body fat stores in obese patients are involved in the pathogenesis of some metabolic disorders (e.g., hyperinsulinaemia, glucose intolerance) and arterial hypertension.. Based on this pathophysiological background, we tried to assess the relationship between plasma leptin and blood pressure in 41 patients with essential hypertension (EHP; 20 females, 21 males, mean age 38.7+/-1.9 years, mean body mass index - BMI - 25.8+/-0.5 kg/m2) and in an appropriately sex- and BMI-matched control group of 27 normotensive healthy subjects (NHS; 11 females, 16 males, mean age 39.7+/-2.5 years, mean BMI 24.8+/-0.6 kg/m2). The plasma leptin concentration did not differ significantly between EHP and NHS (13.0+/-1.9 vs. 8.1+/-1.0 ng/ml, respectively). In both groups a significant positive correlation was found between BMI and plasma leptin concentration (p<0.0001). A significant positive correlation (p<0.02) was found between leptinaemia and mean (MAP), systolic and diastolic blood pressures, if data were analyzed for all examined subjects or separately only for women. Such a correlation could not be confirmed for male NHS and EHP subjects. The plasma neuropeptide Y concentration was higher in EHP than in NHS (77.1+/-23.0 vs. 63.6+/-9.8pg/ml, p = 0.05). In contrast to neuropeptide Y plasma insulin, cortisol, and growth hormone concentrations were similar in EHP and in NHS.. Both EHP and NHS are characterized by a positive correlation between BMI and leptinaemia. Leptin may be indirectly involved in blood pressure regulation, especially in women of both NHS and EHP.

Topics: Adult; Appetite; Blood Pressure; Body Mass Index; Female; Hormones; Humans; Hypertension; Leptin; Male; Neuropeptide Y; Proteins; Sex Characteristics; Sympathetic Nervous System

Although the relationship between an increase in adipose tissue and a rise in blood pressure has long been recognized, the mechanism linking these two phenomena has yet to be fully understood. Recently, it has become evident that adipose tissue is a rich source of metabolically active molecules, including free fatty acids, leptin and angiotensinogen, the precursor of angiotensin II. The latter finding has prompted speculation on the possible role of adipocyte-derived angiotensinogen in the relationship between body weight and blood pressure. Therefore we examined the relationship between blood pressure, angiotensinogen, body mass index (BMI) and leptin levels in healthy normotensive subjects who are genetically predisposed to the development of hypertension.. We studied 40 subjects with a positive family history of hypertension and 51 subjects with a negative family history. After the blood pressure measurements, blood samples were collected for the assessment of angiotensinogen, leptin, glucose, insulin, renin activity and electrolytes. Oral glucose tolerance was studied by an oral glucose tolerance test (75 g glucose).. Plasma angiotensinogen was significantly correlated with both BMI (r=0.29, P < 0.01) and plasma leptin (r=0.40, P < 0.001). While plasma angiotensinogen and blood pressure were positively correlated only in subjects with a positive family history of hypertension (r=0.33, P< 0.05), plasma leptin was related to blood pressure in both groups (r=0.26, P=0.01). Furthermore, the insulin response to an oral glucose load was significantly related to both plasma angiotensinogen (r=0.22, P< 0.05) and plasma leptin (r=0.47, P< 0.001).. These findings support the hypothesis that circulating angiotensinogen levels are related to adipose mass in young, normotensive, nonobese men. Further studies on the relationship between adipose tissue and systemic or local renin-angiotensin systems appear warranted.

Topics: Adipose Tissue; Adult; Angiotensinogen; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Electrolytes; Genetic Predisposition to Disease; Humans; Hypertension; Insulin; Leptin; Male; Proteins; Reference Values; Renin

We studied the effect of induced metabolic syndrome (MetS) on the effectiveness of the infarct-limiting effect of remote ischemic postconditioning (RP) in Wistar rats. The involvement of leptin and corticosterone in the formation of arterial hypertension (AH) and in reduction of the effectiveness of RP in MetS was also studied. MetS was induced by high-carbohydrate high-fat diet with replacement of drinking water with 20% fructose solution for 90 days. MetS simulation led to obesity, AH, impaired lipid and carbohydrate metabolism, hyperleptinemia, and moderate stress. All animals were subjected to 45-min coronary occlusion and 120-min reperfusion. In the RP groups, tourniquets were applied on the hind limbs in the area of the hip joint immediately after the end of ischemia (3 cycles consisting of 5-min ischemia and 5-min reperfusion). A direct correlation was found between the severity of AH in rats with MetS and the levels of corticosterone and leptin. In rats with MetS, the effectiveness of RP decreased: a direct correlation between the infarct size and serum content of leptin was revealed in rats with MetS+RP. Corticosterone seems to be one of the factors of AH development in rats with MetS.

Topics: Animals; Corticosterone; Hypertension; Infarction; Ischemia; Ischemic Postconditioning; Leptin; Metabolic Syndrome; Myocardial Reperfusion Injury; Rats; Rats, Wistar

The mechanisms link obesity and hypertension are not well understood. One possibility is the alterations in adipose-derived adipokines that modulate insulin resistance (IR) and cardiovascular homeostasis. We aimed to assess the associations between hypertension and four adipokine levels in Chinese youth, and to examine to what extent the associations are mediated by IR. We utilized cross-sectional data from the Beijing Children and Adolescents Metabolic Syndrome (BCAMS) Study Cohort (n = 559, mean age = 20.2 years). Plasma leptin, adiponectin, retinol binding protein 4 (RBP4) and fibroblast growth factor 21 (FGF21) levels were assayed. The relationships between adipokines and hypertension and the possible mediation effect of IR were evaluated. Youth with hypertension have lower adiponectin and higher leptin, FGF21 (all P < 0.001) and RBP4 levels (p = 0.06) compared to their counterparts. Moreover, the co-existence of these two or more adipokine abnormalities in youth leads to a 9-fold increased risk for hypertension (OR: 9.19; 95% CI, 4.01-21.08) compared with these without abnormalities. However, in the fully adjusted and BMI-adjusted analyses, only FGF21 was a significant predictor of hypertension (OR: 2.12; 95% CI, 1.34-3.36). Mediation analysis revealed that the associations between leptin, adiponectin, RBP4 and hypertension are totally mediated by IR (proportion: 63.9%, 65.4%, and 31.6%, respectively), while BMI and IR partly mediated the association between FGF21 and hypertension (proportion: 30.6%, 21.2%). Our findings suggest that dysregulation of adipokines might result in hypertension in youth. Leptin, adiponectin and RBP4 may exert their functions in hypertension through adiposity-related IR, whereas FGF21 might be used as an independent marker of hypertension in youth.

Topics: Adipokines; Adiponectin; Adolescent; Beijing; Child; Cross-Sectional Studies; Humans; Hypertension; Insulin Resistance; Leptin; Obesity; Retinol-Binding Proteins, Plasma; Young Adult

The aim: Study of the levels of leptin and the growth modulator TGF-β1 in the blood serum of patients with hypertension, which occurs on the background of AO and without it.. Materials and methods: Carbohydrate metabolism was studied by the enzymatic method, the level of insulin in the blood (by the enzyme immunoassay method), the oral glucose tolerance test and the calculation of the NOMA index.. Results: The data obtained in the work indicate a significant role of leptin in the formation of hypertension itself and the development of obesity, carbohydrate and lipid metabolism disorders. The increased level of transforming growth factor-β1 in the blood of such patients can be used as a fairly informative marker of the unfavorable prognosis of these diseases.. Conclusions: 1. In the control group, there was a significant increase in the initial values of heart rate, average levels of SBP and DBP, the frequency of hy-percholesterolemia and insulin resistance was established. 2. Significant disorders of lipid and carbohydrate metabolism and leptin synthesis were found in patients with hypertension, which occurs against the background of AO. 3. When analyzing the level of leptin depending on gender, a statistically significant increase in the level of blood leptin was found in the group of women with AH with AO compared to women with AH without AO and the control group. 4. A significant increase in the level of transforming growth factor-β1 in blood serum of patients with hypertension was established.

Topics: Female; Humans; Hypertension; Leptin; Obesity; Obesity, Abdominal; Serum; Transforming Growth Factor beta1

Inflammation has been associated with vascular access (VA) dysfunction. The adipocytokine leptin can directly induce pro-inflammatory T helper 1 immune responses and the pathogenesis of chronic inflammation. We explored the association between plasma leptin and VA dysfunction in patients on maintenance hemodialysis (HEMO).. A total of 344 consecutive patients who received anastomosis for VA at a single HEMO center between June 1, 2010 and December 31, 2021 were screened. Of these patients, 267 met the inclusion criteria and were included. ELISA was used to measure circulating levels of leptin.. The VA dysfunction group had a higher leptin level than the patent VA group. A higher concentration of leptin was independently and significantly associated with an elevated risk of VA dysfunction. Multiple logistic regression analysis showed that leptin, female sex, and hypertension were independently associated with VA dysfunction, even after adjusting for known biomarkers. We then evaluated the ability of leptin, female sex, and hypertension to predict the risk of VA dysfunction, and the area under the curve (AUC) for leptin was 0.626 (p = 0.0001). When leptin, female sex, and hypertension were added to this multivariate model, the AUC increased to 0.679 (p = 0.001) for leptin and hypertension, and 0.690 for leptin, hypertension, and female sex (p = 0.004). In addition, plasma leptin levels were associated with sex, body mass index, and hemoglobin.. In addition to the association between leptin and VA dysfunction, hypertension and female sex independently predicted VA dysfunction in patients with HEMO.

Topics: Biomarkers; Body Mass Index; Female; Humans; Hypertension; Inflammation; Leptin; Renal Dialysis

Prolonged high-fat diet (HFD) accelerates the cardiovascular, renal, and metabolic dysfunction in hypertensive rats with altered renal development (ARDev). Soluble guanylate cyclase (sGC) stimulation or sodium-glucose cotransporter 2 (SGLT2) inhibition may improve cardiovascular, renal, and metabolic function in settings of hypertension and obesity. This study examined whether 6 wk treatment with an SGLT2 inhibitor (empagliflozin, 7 mg/kg/day) enhances the cardiovascular, renal, and metabolic effects of a sGC stimulator (praliciguat, 10 mg/kg/day) in hypertensive rats with ARDev and prolonged exposure to HFD. Arterial pressure (AP), renal vascular resistance (RVR), fat abdominal volume (FAV), insulin resistance, leptin and triglycerides levels, and intrarenal infiltration of inflammatory cells were higher, but cardiac output and creatinine clearance were lower in hypertensive rats (

Topics: Animals; Benzhydryl Compounds; Creatinine; Diet, High-Fat; Glucose; Hypertension; Insulin Resistance; Leptin; Rats; Sodium-Glucose Transporter 2; Soluble Guanylyl Cyclase; Triglycerides

Patients with preeclampsia demonstrate increases in placental leptin production in midgestation, and an associated increase in late gestation plasma leptin levels. The consequences of mid-late gestation increases in leptin production in pregnancy is unknown. Our previous work indicates that leptin infusion induces endothelial dysfunction in nonpregnant female mice via leptin-mediated aldosterone production and endothelial mineralocorticoid receptor (ECMR) activation, which is ablated by ECMR deletion. Therefore, we hypothesized that leptin infusion in mid-gestation of pregnancy induces endothelial dysfunction and hypertension, hallmarks of clinical preeclampsia, which are prevented by ECMR deletion.. Leptin was infused via miniosmotic pump (0.9 mg/kg per day) into timed-pregnant ECMR-intact (WT) and littermate-mice with ECMR deletion (KO) on gestation day (GD)11-18.. Leptin infusion decreased fetal weight and placental efficiency in WT mice compared with WT+vehicle. Radiotelemetry recording demonstrated that blood pressure increased in leptin-infused WT mice during infusion. Leptin infusion reduced endothelial-dependent relaxation responses to acetylcholine (ACh) in both resistance (second-order mesenteric) and conduit (aorta) vessels in WT pregnant mice. Leptin infusion increased placental ET-1 (endothelin-1) production evidenced by increased PPET-1 (preproendothelin-1) and ECE-1 (endothelin-converting enzyme-1) expressions in WT mice. Adrenal aldosterone synthase (. Collectively, these data indicate that leptin infusion in midgestation induces endothelial dysfunction, hypertension, and fetal growth restriction in pregnant mice, which is ablated by ECMR deletion.

Topics: Animals; Blood Pressure; Endothelin-1; Female; Humans; Hypertension; Leptin; Mice; Mice, Knockout; Placenta; Pre-Eclampsia; Pregnancy; Receptors, Mineralocorticoid

To explore the role of leptin in the onset and development of obesity-associated hypertension.. A case-control study that had finished recruiting 153 subjects divided as four characteristic groups. Leptin serum levels were tested by ELISA in these subjects among these four characteristic Chinese adult physical examination groups. Waist circumference (WC), body mass index (BMI), systolic blood pressure (SB), diastolic blood pressure (DB), and other clinical laboratory data were collected. Analyzation of correlations between the research index and differences between groups was done by SPSS.. Serum leptin levels statistically significantly positively correlated with BMI and WC, and negatively with the HDLC (high-density lipoprotein cholesterol), even after adjustment for age and gender. There was no significant difference in the serum leptin levels between the normal healthy group (NH group) and the newly diagnosed untreated just-hypertension group (JH group). And the same is between the newly diagnosed untreated obesity-hypertension group (OH group) and the newly diagnosed untreated just-obesity group (JO group). Multiple linear regression analysis indicated BMI and gender as significant independent correlates of serum leptin.. These results show leptin may not be essential but play an additive effect in the development of obesity-associated hypertension. Leptin may only play an additive effect role in the intricate interwoven network of regulators contributing to the development of hypertension in obese patients.

Topics: Adult; Body Mass Index; Case-Control Studies; China; Humans; Hypertension; Leptin; Obesity

Leptin plays a crucial role in blood pressure (BP) regulation, notably in the context of obesity through central sympatho-mediated pressor effects. Leptin also relaxes arteries via endothelial (EC) leptin receptor (LepR

Topics: Adrenergic Agents; Animals; Endothelium; Hypertension; Leptin; Male; Mice; Nitric Oxide; Obesity; Receptors, Leptin

Topics: Endocarditis; Humans; Hypertension; Hypertension, Pulmonary; Leptin; Pulmonary Valve

Plasma leptin is considered a risk factor for obesity and cardio-metabolic disease, but the link between serum leptin and renal function is still under evaluation. In our study, we focused on the relationship between serum leptin and renal function, and we investigated the relationship in more detail.. The 396 middle-aged and elderly Taiwanese adults recruited for our health survey were the subject of our research. All participants agreed to participate and signed a consent form before they joined and completed our study. We divided the participants into three groups according to eGFR tertiles and analyzed the parameters between each group. Then, we used Pearson's correlation test to investigate the relationship between eGFR levels and cardio-metabolic risk factors with adjustment for age. The scatter plot indicates the trend between serum leptin levels and eGFR levels. Participants were reclassified into three subgroups according to their leptin levels and the bar chart reveals the prevalence of chronic kidney disease (CKD) in each group. Finally, we used multivariate linear regression to evaluate the relationship between serum leptin and eGFR levels with adjustment for age, sex, smoking status, drinking status, body mass index (BMI), uric acid levels, hypertension (HTN), diabetes mellitus (DM), and dyslipidemia.. In our study, we analyzed the data from 396 eligible participants. A total of 41.4% of the participants were male, and the average age of all participants was 64.81 years ( ± 8.78). The participants in the high eGFR group were more likely to have lower serum leptin levels. Furthermore, eGFR values were negatively correlated with serum leptin levels even after adjustment for age. The prevalence of CKD in the high serum leptin group was higher than that in the low serum leptin group. Serum leptin levels showed significant negative correlations with eGFR levels (β=-0.14, p<0.01) in the multivariate linear regression after adjusting for age, sex, smoking status, drinking status, BMI, uric acid levels, HTN, DM, and dyslipidemia.. According to our study, serum leptin levels show a negative relationship with eGFR levels in middle-aged and elderly people in Taiwan. In addition, high serum leptin levels could be an novel marker to survey kidney failure in clinical practices.

Topics: Adult; Aged; Cross-Sectional Studies; Diabetes Mellitus; Female; Humans; Hypertension; Kidney; Leptin; Male; Middle Aged; Renal Insufficiency, Chronic; Taiwan; Uric Acid

Neurodegeneration is associated with hypertension and disturbance in fat metabolism. The complex interaction of neurodegenerative processes with both metabolic changes and blood pressure is still not fully elucidated. Here we demonstrate that the experimentally induced tauopathy in hypertensive transgenic animals causes significant downregulation of plasma leptin (53% of control), reduction of body weight by 11%, a 1.2-fold drop of adiposity index, and decrease in HDL cholesterol level, while the fasting glucose and insulin concentration remain unchanged. Despite of these alterations we found the leptin projection circuit including the arcuate nucleus, paraventricular nucleus in hypothalamus, and nucleus tractus solitarius in the brainstem not affected by neurofibrillary pathology. Furthermore, hypertension does not alter disturbances in leptin signalling. The presented data provide further insight into neurodegeneration-induced metabolic alterations relevant for human tauopathies.

Topics: Animals; Arcuate Nucleus of Hypothalamus; Humans; Hypertension; Leptin; Models, Theoretical; Tauopathies

The aim: To compare lipid metabolism and leptin levels among the children with and without hypertension to identify associated risk factors for the course of metabolic syndrome in children.. Materials and methods: This observational, cross-sectional study recruited children from the Rheumocardiology Department of Children's Clinical Hospital No 6 in Kyiv, with metabolic syndrome, identification of waist-to-height ratio, leptin level, homeostasis model assessment of insulin resistance and lipid profile. The main group included 41 children with metabolic syndrome and hypertension and the control group included 40 children with metabolic syndrome without hypertension. Statistical data analysis was performed using the MedStat 2.6.2. package.. Results: A total of 81 children aged 10 to 17 with metabolic syndrome were examined. The group of children with hypertension had significantly lower high-density lipoprotein cholesterol (0.85±0.04) than children without hypertension (0.94±0.03), with p < 0.05. Leptin resistance was detected in 65.2% of children with hypertension and 35.3% of children with normal blood pressure (p < 0.01).. Conclusions: Children with metabolic syndrome and hypertension had a significantly higher body mass index and waist circumference as opposed to children with normal blood pressure. In the lipid profile high-density lipoprotein cholesterol was significantly lower in hypertensive children. There was no reliable difference in other lipid profile indicators between the two groups, but there was an upward trend of them in group with hypertension. Leptin resistance is also significantly higher in hypertensive children.

Topics: Child; Cross-Sectional Studies; Humans; Hypertension; Leptin; Lipids; Metabolic Syndrome; Ukraine

This study aimed to investigate whether the antihypertensive effect of irbesartan (IRB) in spontaneously hypertensive rats (SHR) was achieved through improvement of insulin resistance and adjustment of the LPN-APN imbalance.. The antihypertensive effect of IRB in SHR rats was associated with its improvement of insulin resistance and correction of the LPN-APN imbalance.

Topics: Adiponectin; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Blood Pressure; Hypertension; Irbesartan; Leptin; Male; Rats; Rats, Inbred SHR; Rats, Inbred WKY

[Figure: see text].

Topics: Black People; Blood Pressure; Blood Pressure Determination; Body Mass Index; C-Reactive Protein; Cholesterol; Disease Progression; Female; Humans; Hypertension; Incidence; Leptin; Longitudinal Studies; Male; Middle Aged; Obesity; Risk Factors; United States

Denervation of renal sympathetic nerves (RDN) is an invasive endovascular procedure introduced as an antihypertensive treatment with a potential beneficial effect on insulin resistance (IR). We have previously demonstrated a reduction in blood pressure (BP) six months after RDN, but severe hepatic and peripheral IR, assessed by glucose tracer and two step hyperinsulinemic-euglycemic clamp (HEC), did not improve. The aim of the current study was to evaluate IR and adipokines profiles in relation to BP and arterial stiffness changes two years after RDN.. In 20 non-diabetic patients with true treatment-resistant hypertension, ambulatory and office BP were measured after witnessed intake of medications prior to, six and 24 months after RDN. Arterial stiffness index (AASI) was calculated from ambulatory BP. Insulin sensitivity (IS) was assessed using an oral glucose tolerance test (OGTT), the Homeostasis Model Assessment (HOMA-IR), HOMA-Adiponectin Model Assessment (HOMA-AD), the Quantitative Insulin Sensitivity Check Index (QUICKI), the Triglyceride and Glucose Index (TyG) and the Leptin-to-Adiponectin Ratio (LAR). These surrogate indices of IS were compared with tracer/HEC measurements to identify which best correlated in this group of patients.. All measured metabolic variables and IS surrogate indices remained essentially unchanged two years after RDN apart from a significant increase in HOMA-AD. OGTT peak at 30 min correlated best with reduction in endogenous glucose release (EGR) during low insulin HEC (r = -0.6, p = 0.01), whereas HOMA-IR correlated best with whole-body glucose disposal (WGD) (r = -0.6, p = 0.01) and glucose infusion rate (r = -0.6, p = 0.01) during high insulin HEC. BP response was unrelated to IS prior to RDN. Nocturnal systolic BP and arterial stiffness before RDN correlated positively with a progression in hepatic IR at six-month follow-up.. IR, adiponectin and leptin did not improve two years after RDN. There was no correlation between baseline IS and BP response. Our study does not support the notion of a beneficial metabolic effect of RDN in patients with treatment resistant hypertension.

Topics: Adiponectin; Biomarkers; Blood Glucose; Blood Pressure; Denervation; Female; Follow-Up Studies; Glucose Clamp Technique; Glucose Tolerance Test; Health Status Indicators; Humans; Hypertension; Insulin; Insulin Resistance; Kidney; Leptin; Male; Middle Aged; Postoperative Period; Time Factors; Treatment Outcome; Vascular Stiffness

The aim: To evaluate anthropometric, hemodynamic parameters, as well as changes in blood and leptin lipid spectrum in children and adults with overweight and obesity.. Materials and methods: We examined 68 overweight children and 90 patients with obesity in combination with stage 2, grade 2 AH who were electively inpatient. The control group consisted of practically healthy individuals - 20 adults and 55 children.. Results: Obesity in childhood isaccompanied by the development of dyslipidemia, hypercholesterolemia, hyperleptinemia and hypertension, and in adulthood may be an additional risk factor for cardiovascular disease, in particular AH. According to the study, total leptin level in overweight children was significantly higher compared to the control group (p<0.01). The concentration of leptin in patients with hypertension in combination with obesity was 3 times higher compared to the control group (p<0.01).. Conclusions: Thus, obesity or overweight, accompanied by hyperleptinemia and an increase in the proatherogenic fractions of the blood lipid spectrum, is an important problem that needs to be addressed in childhood to prevent cardiovascular disease in adulthood.

Topics: Adult; Body Mass Index; Child; Humans; Hypertension; Leptin; Metabolic Syndrome; Overweight; Pediatric Obesity; Risk Factors

Pathologies of the micro- and macrovascular systems are a hallmark of the metabolic syndrome, which can lead to chronically elevated blood pressure. However, the underlying pathomechanisms involved still need to be clarified. Here, we report that an obesity-associated increase in serum leptin triggers the select expansion of the micro-angioarchitecture in pre-autonomic brain centers that regulate hemodynamic homeostasis. By using a series of cell- and region-specific loss- and gain-of-function models, we show that this pathophysiological process depends on hypothalamic astroglial hypoxia-inducible factor 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling downstream of leptin signaling. Importantly, several distinct models of HIF1α-VEGF pathway disruption in astrocytes are protected not only from obesity-induced hypothalamic angiopathy but also from sympathetic hyperactivity or arterial hypertension. These results suggest that hyperleptinemia promotes obesity-induced hypertension via a HIF1α-VEGF signaling cascade in hypothalamic astrocytes while establishing a novel mechanistic link that connects hypothalamic micro-angioarchitecture with control over systemic blood pressure.

Topics: Animals; Astrocytes; Female; Hypertension; Hypothalamus; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity

[Figure: see text].

Topics: Animals; Blood Pressure; Carotid Body; Fingolimod Hydrochloride; Hydrogels; Hypertension; Immunosuppressive Agents; Leptin; Male; Mice, Inbred C57BL; Mice, Knockout; Obesity; RNA Interference; TRPM Cation Channels

Topics: Epigenome; Humans; Hypertension; Leptin; Obesity

The aim - to analyze the relationship between leptin levels and morphometric, anthropometric, biochemical parameters in patients with hypertension and obesity and in healthy individuals. The study included 64 patients with obesity and hypertension and 21 healthy individuals. The groups were comparable in age and gender. Leptin was determined by enzyme immunoassay method. Data are presented as mean values and the error of the mean (M±m). Differences were considered statistically significant at p<0,05. It was found out a strong positive correlation in the group with hypertension and obesity between plasma leptin levels and total cholesterol (r=0.40, p=0.00004), strong negative correlation between leptin and HDL (r=-0 , 43, p=0.0005), uric acid (r=0.32 p=0.00092) and ionized calcium levels (r=-0.35 p=0.00027). Leptin levels in the group of healthy individuals correlated with a waist circumference (r=0.78, p=0.005), BFM, BMI and age (r=0.92, r=0.94, r=0.81, p<0 , 05), uric acid levels (r=0.94) and ionized calcium (r=0.91) at p<0.05. The present study provides evidence that BFM, TG, HDL, VLDL, atherogenic index, ionized calcium levels and uric acid have a significant impact on serum leptin in patients with hypertension and obesity.

Topics: Body Mass Index; Humans; Hypertension; Leptin; Obesity; Waist Circumference

This study examines the long-term functional effects of d-fagomine on sucrose-induced factors of metabolic dysfunctions and explores possible molecular mechanisms behind its action.. Wistar Kyoto rats are fed a 35% sucrose solution with d-fagomine (or not, for comparison) or mineral water (controls) for 24 weeks. The following are recorded: body weight; energy intake; glucose tolerance; plasma leptin concentration and lipid profile; populations of Bacteroidetes, Firmicutes, bacteroidales, clostridiales, enterobacteriales, and Escherichia coli in feces; blood pressure; urine uric acid and F. d-fagomine counteracts sucrose-induced steatosis and hypertension, presumably by reducing the postprandial levels of fructose in the liver.

Topics: Adipose Tissue; Animals; Diglycerides; Energy Intake; Fagopyrum; Gastrointestinal Microbiome; Hypertension; Imino Pyranoses; Isoprostanes; Leptin; Lipids; Liver; Male; Non-alcoholic Fatty Liver Disease; Postprandial Period; Rats, Inbred WKY; Sucrose; Uric Acid

Sex differences in heart failure with preserved ejection fraction (HFpEF) have been established, but insights into the mechanistic drivers of these differences are limited.. To examine sex differences in cardiometabolic profiles and exercise hemodynamic profiles among individuals with HFpEF.. This cross-sectional study was conducted at a single-center tertiary care referral hospital from December 2006 to June 2017 and included 295 participants who met hemodynamic criteria for HFpEF based on invasive cardiopulmonary exercise testing results. We examined sex differences in distinct components of oxygen transport and utilization during exercise using linear and logistic regression models. The data were analyzed from June 2018 to May 2019.. Resting and exercise gas exchange and hemodynamic parameters obtained during cardiopulmonary exercise testing.. Of 295 participants, 121 (41.0%) were men (mean [SD] age, 64 [12] years) and 174 (59.0%) were women (mean [SD] age, 61 [13] years). Compared with men, women with HFpEF in this tertiary referral cohort had fewer comorbidities, including diabetes, insulin resistance, and hypertension, and a more favorable adipokine profile. Exercise capacity was similar in men and women (percent predicted peak oxygen [O2] consumption: 66% in women vs 68% in men; P = .38), but women had distinct deficits in components of the O2 pathway, including worse biventricular systolic reserve (multivariable-adjusted analyses: ΔLVEF β = -1.70; SE, 0.86; P < .05; ΔRVEF β = -2.39, SE=0.80; P = .003), diastolic reserve (PCWP/CO: β = 0.63; SE, 0.31; P = .04), and peripheral O2 extraction (C(a-v)O2 β=-0.90, SE=0.22; P < .001)).. Despite a lower burden of cardiometabolic disease and a similar percent predicted exercise capacity, women with HFpEF demonstrated greater cardiac and extracardiac deficits, including systolic reserve, diastolic reserve, and peripheral O2 extraction. These sex differences in cardiac and skeletal muscle responses to exercise may illuminate the pathophysiology underlying the development of HFpEF and should be investigated further.

Topics: Adipokines; Adiponectin; Aged; C-Reactive Protein; Cardiometabolic Risk Factors; Diabetes Mellitus; Exercise Test; Exercise Tolerance; Female; Heart Failure; Humans; Hypertension; Insulin Resistance; Interleukin-6; Leptin; Linear Models; Logistic Models; Male; Middle Aged; Obesity; Oxygen Consumption; Pulmonary Gas Exchange; Sex Factors; Stroke Volume

Leptin is associated with cardiovascular risk factors (e.g. hypertension, insulin resistance, kidney disease and excess body weight). Experimental studies showed that leptin might affect serum uric acid, by modulation of the uric acid excretion. However, there are few observational data on the relationship between leptin and uric acid in the general population. Therefore, the aim of the present study was to evaluate the relationship between leptin and uric acid and its excretion in a large middle-aged male general population.. A sample of 930 adult male individuals (mean age: 52 years) without therapy for high uric acid was included in the analysis (the Olivetti Heart Study).. Uric acid was significantly and positively associated with blood pressure, BMI, waist circumference, insulin resistance, C-reactive protein and leptin (p < 0.01), while inversely with renal function (p = 0.01). The multivariate analysis confirmed the association between leptin and uric acid after adjustment for potential confounders (p < 0.01). After division for adiposity, this trend was confirmed separately for normal weight and excess body weight participants. Moreover, leptin was inversely associated with excretion of uric acid (p < 0.01), also in multivariate analysis (p = 0.03).. The results of this study indicate a positive association between circulating leptin levels and uric acid, independently of potential confounders, both in normal and excess body weight men. Furthermore, an inverse association between leptin and uric acid excretion was detected.

Topics: Adult; Blood Pressure; Body Mass Index; C-Reactive Protein; Humans; Hypertension; Insulin Resistance; Kidney; Kidney Function Tests; Leptin; Male; Middle Aged; Obesity; Overweight; Risk Factors; Uric Acid; Waist Circumference

Cardiovascular disease (CVD) is a leading cause of mortality in nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the relationship of leptin-to-adiponectin (L/A) ratio with hepatic steatosis and arterial stiffness in NAFLD.. The subjects were 871 Japanese adults who participated in a health survey. Dietary intake, body composition, lipid profile, serum interleukin-6 (IL-6), leptin, and adiponectin were analyzed. NAFLD was defined as fatty liver on ultrasonography in the absence of other causes of steatosis. Arterial stiffness was evaluated by the brachial-ankle pulse wave velocity (baPWV).. The subjects with NAFLD had a greater body mass index (BMI) and body fat percentage (BFP); a higher intake of daily energy (kcal) and carbohydrates; and a higher prevalence of hypertension, diabetes, and hyperlipidemia. The subjects with NAFLD had higher serum leptin and lower serum adiponectin concentrations and a higher L/A ratio than subjects without NAFLD. The L/A ratio increased with increasing severity of steatosis. The L/A ratio showed positive correlations with BMI and BFP, and a negative correlation with age. Women had higher L/A ratio and BFP levels than men regardless of the presence or absence of NAFLD. There was a weak positive correlation between baPWV and severity of steatosis. BaPWV was strongly correlated with age, while no relation was found between baPWV and L/A ratio. IL-6 level was correlated with baPVW and age, while the correlation between Il and 6 level and L/A ratio was very weak. The L/A ratio was correlated with triglycerides and the ratio of total cholesterol to high-density lipoprotein-cholesterol.. L/A ratio and arterial stiffness were associated with the severity of steatosis, whereas there was no correlation between L/A ratio and arterial stiffness in NAFLD. These findings suggest that not only leptin and adiponectin but also other factors might be involved in the pathogenesis for atherosclerosis in NAFLD.

Topics: Adiponectin; Ankle Brachial Index; Blood Pressure; Body Mass Index; Cardiovascular Diseases; Diet; Female; Humans; Hypertension; Interleukin-6; Japan; Leptin; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Surveys and Questionnaires; Vascular Stiffness

Topics: Animals; Antihypertensive Agents; Autocrine Communication; Hypertension; Leptin; Male; Myocardium; PPAR gamma; Rats; Rats, Sprague-Dawley; Telmisartan; Ventricular Remodeling

Parental high-fat diet (HFD) programs for obesity and hypertension in female offspring in rats, but it is unknown how the pregnancies of these offspring are impacted. Therefore, the hypothesis was tested that parental HFD exaggerates obesity and hypertension during pregnancy of the offspring. Wistar Hannover rat dams (the parental, P generation) were maintained on normal-fat diet (NFD) or HFD from weaning and were kept on respective diets through pregnancy and lactation. Their offspring (the first filial, F1 generation) were weaned onto the same diet as the P generation, or they were changed to the other diet to determine if combined HFD in the P and F1 generations exaggerates body weight and blood pressure levels during pregnancy in these offspring. This diet paradigm resulted in the following groups of pregnant F1 offspring: P-NFD/F1-NFD, P-HFD/F1-NFD, P-NFD/F1-HFD, and P-HFD/F1-HFD. Maternal body and adipose tissue weights were greatest in the P-HFD/F1-HFD group compared to the other 3 groups by the end of pregnancy. Plasma leptin and conscious mean arterial blood pressure were not significantly different between any group, although there was a main effect for increased blood pressure in the F1-HFD groups. Circulating levels of the antihypertensive pregnancy factor, placental growth factor (PlGF), were assessed. Although average PlGF levels were similar among all groups, correlative studies revealed that lower levels of PlGF were associated with higher blood pressure only in the P-HFD/F1-HFD group. In summary, HFD feeding from the P generation exaggerated HFD-induced body and adipose tissue weights in the pregnant offspring.

Topics: Adiposity; Animals; Blood Pressure; Body Weight; Diet, High-Fat; Disease Models, Animal; Female; Humans; Hypertension; Leptin; Male; Maternal Inheritance; Obesity; Placenta Growth Factor; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Weaning

Topics: Adult; Blood Pressure; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Diastole; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Sex Factors; Systole

Topics: Carotid Body; Humans; Hypertension; Leptin; Obesity; Protein Serine-Threonine Kinases; TRPM Cation Channels

Hypertension is a common cardiovascular disease in clinical scenario. The level of leptin changes with the development of hypertension and is regulated by Aldehyde dehydrogenase2 (ALDH2). Our study explored the relationship between irbesartan treatment and ALDH2. Spontaneously hypertensive rats were treated with irbesartan solution and ALDH2 over expression adenovirus vector for experimental group, and the equivalent amount of spontaneously hypertensive rats was treated with irbesartan solution and null adenovirus vector for control group. Sham group included spontaneously hypertensive rats treated with saline solution and null adenovirus vector. Pathological change of cardiac muscle tissue was observed with microscope. N-terminal Pro-brain natriuretic peptide, blood pressure, left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS) and renal function were assessed to determine cardiovascular function. Expression of serum leptin and mRNA of leptin were examined, respectively. ALDH2 was confirmed by western blot examination. Statistical Analysis was performed to determine correlation. Compared with sham group, ALDH2 were decreased significantly in control group. Remarkable pathological changes of cardiovascular and renal injury were observed in control group rats, including increased NT-proBNP, renal interstitial fibrosis and aberrant hypertension. Compared with control group, experimental group had lower levels of blood pressure and NT-proBNP, but higher level of Glomerular Filtration Rate (GFR). Moreover, irbesartan -treated rats had significantly higher levels of leptin, suggesting irbesartan treatment ameliorated symptoms of hypertension. Expression of serum leptin had a negative correlation with mRNA of leptin (P<0.05). Moreover, compared with control group, ALDH2 over expression significantly improved irbesartan treatment, verified by hypertension related index. Decreased ALDH2 expression were correlated with progression of hypertension. Rats with Hypertension indeed benefited from irbesartan treatment. ALDH2 elevated the drug susceptibility of irbesartan treatment for hypertension via regulating serum leptin, and improved efficacy of irbesartan treatment on hypertension.

Topics: Aldehyde Dehydrogenase, Mitochondrial; Animals; Antihypertensive Agents; Gene Expression Regulation; Hypertension; Irbesartan; Leptin; Male; Rats; Rats, Inbred SHR; Rats, Wistar; Up-Regulation

Variation in blood flow mediated by the posterior communicating collateral arteries (PComs) contributes to variation in the severity of tissue injury in obstructive disease. Evidence in animals and humans indicates that differences in the extent of PComs, i.e., their anatomic lumen diameter and whether they are present bilaterally, unilaterally, or absent, are a major factor. These differences arise during development since they are present at birth. However, the causal mechanisms are unknown. We used angiography after maximal dilation to examine involvement of genetic, environmental, and stochastic factors. The extent of PComs varied widely among seven genetically diverse strains of mice. Like pial collaterals in the microcirculation, aging and hypertension reduced PCom diameter, while in contrast, obesity, hyperlipidemia, metabolic syndrome, and diabetes mellitus had no effect. Naturally occurring intrauterine growth restriction had no effect on extent of PCom or pial collaterals in the adult. The number and diameter of PComs evidenced much larger apparent stochastic-dependent variation than pial collaterals. In addition, both PComs underwent flow-mediated outward remodeling after unilateral permanent MCA occlusion that varied with genetic background and was greater on the ipsilesional side. These findings indicate that variation in the number and diameter of PCom collateral arteries arises from stochastic factors and naturally occurring genetic variants that differ from those that cause variation in pial collateral arterioles. Environmental factors also contribute: aging and hypertension reduce PCom diameter. Our results suggest possible sources of variation of PComs in humans and provide information relevant when studying mouse models of occlusive cerebrovascular disease.

Topics: Aging; Animals; Apolipoproteins E; Cerebrovascular Circulation; Circle of Willis; Collateral Circulation; Disease Models, Animal; Glucose Metabolism Disorders; Hypertension; Leptin; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Transgenic; Mutation; Renin

The incidence of hypertension and diabetes is increasing, it is reported that adipocytokines might be involved in the pathogenesis of diabetes and hypertension. We aimed to investigate the features of adipocytokines, included of Leptin, Irisin, LGR4, and Sfrp5 in type 2 diabetes mellitus (T2DM) patients with hypertension, simultaneously analyzed the connection of the alteration of adipocytokines with blood pressure and glucose. 424 patients with T2DM and 90 healthy subjects were included in the study. The patients with T2DM were divided into 4 groups based on the blood pressure. The levels of adipocytokines (Leptin, Irisin, LGR4, and Sfrp5) were determined by enzyme-linked immunosorbent assay (ELISA). Significantly higher levels of Leptin and lower levels of Irisin, LGR4 and Sfrp5 were seen in patients with diabetes compared with non-diabetes (P < 0.05), the mean values of Leptin level was ascending and Irisin, LGR4, and Sfrp5 levels were declining with promoting of blood pressure in hypertension as compared to the non-hypertension with diabetic patients. Multiple stepwise linear regression analysis showed that the concentrations of Leptin, Irisin, Sfrp5, and LGR4 were found to be closely associated with the control of blood pressure and glucose.

Topics: Adaptor Proteins, Signal Transducing; Adipokines; Adult; Aged; Blood Glucose; Blood Pressure; Case-Control Studies; Diabetes Mellitus, Type 2; Eye Proteins; Female; Fibronectins; Humans; Hypertension; Leptin; Male; Membrane Proteins; Middle Aged; Receptors, G-Protein-Coupled

Topics: Adolescent; Adult; Blood Pressure; Body Mass Index; Diabetes Mellitus; Dyslipidemias; Female; Follow-Up Studies; Gastrectomy; Ghrelin; Humans; Hypertension; Laparoscopy; Leptin; Male; Middle Aged; Obesity, Morbid; Postoperative Period; Preoperative Period; Prospective Studies; Sleep Apnea, Obstructive; Time Factors; Treatment Outcome; Weight Loss; Young Adult

Mounting evidence shows that adiposity is closely related to elevated blood pressure (BP); however, the underlying mechanism of this relationship is not clearly understood. We aimed to assess the mediating effects of an inflammatory factor (high sensitivity C-reactive protein, hsCRP) and adipokines, as well as any sex differences, on the relationship between adiposity and BP among Chinese overweight or obese adults. A total of 1221 overweight or obese subjects aged 20-55 years who lived in Beijing for at least 1 year were recruited in 2014. The percentage of body fat (PBF) was examined using dual energy X-ray absorptiometry (DXA). Mediation analyses were conducted to examine the mediation of hsCRP, leptin, and adiponectin on the relationship between adiposity and BP by sex. Serum hsCRP and leptin levels were positively associated with PBF (P < 0.001) in males and females. Adiponectin and leptin levels were associated with systolic BP (SBP), but only in males, while in females, the hsCRP level was associated with SBP and diastolic BP (DBP). In males, leptin mediated 22.5% of the relationship between adiposity and SBP and 31.4% for DBP (mediation effect = 0.059 and 0.068, respectively, P < 0.05). However, in females, hsCRP mediated 30.2% of the relationship between adiposity and SBP and 29.5% for DBP (mediation effect = 0.058 and 0.063, respectively, P < 0.001). There are sex differences in the mediation roles of hsCRP and adipokines on the relationship between adiposity and BP. Leptin mediated part of the relationship between adiposity and BP in males, while hsCRP mediated the relationship in females. Our results provide evidence for adiposity-related high BP control measures in a sex-specific manner and provide hints for exploring the potential mechanisms of obesity-related hypertension.

Topics: Absorptiometry, Photon; Adipokines; Adiposity; Adult; Blood Pressure; Body Composition; C-Reactive Protein; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Overweight; Sex Characteristics; Young Adult

Obesity increases the risk of developing hypertension. Since both pathological entities constitute public health problems, the aim of this study was to investigate RNA expression of adiponectin, leptin and their receptors in adipose tissue in women with class 3 obesity, with or without hypertension. Serum concentrations of these adipokines were also quantitated. Women with obesity and hypertension (n = 22) and with obesity without hypertension (n = 37) were included. All patients presented class 3 obesity, without diabetes mellitus. The expression of mRNA in: adiponectin, ADIPOR1 and ADIPOR2 was analyzed in visceral (VAT) and subcutaneous (SAT) adipose tissue; leptin and its receptor were only analyzed in SAT, by reverse transcription quantitative PCR. Measurements of adiponectin and leptin concentrations were performed using enzyme-linked immunosorbent assay kits. Analysis of mRNA expressions in VAT and SAT are presented as median and quartiles. Analysis of serum concentrations of adipokines are presented as median and percentiles 25th-75th. Women presenting a higher mean arterial pressure, had significantly higher levels of mRNA expression of adiponectin in SAT. Besides, we found several significant positive correlations of these adipokines and their receptors. In conclusion, we found that those women with a higher mean arterial pressure and receiving antihypertensive treatment, presented higher levels of mRNA expression of adiponectin in SAT.

Topics: Adiponectin; Adipose Tissue; Adult; Female; Humans; Hypertension; Intra-Abdominal Fat; Leptin; Obesity; Receptors, Adiponectin; RNA, Messenger; Subcutaneous Fat

To investigate the association between serum leptin concentration with blood pressure and hypertension in different gender.. A total of 343 non-hypertensive residents aged 30 to 65 were randomly selected from Zhejiang Province in 2014. Parameters including height, weight, waist, blood pressure, serum lipid and serum leptin concentration of participants were measured and determined by physical examination and laboratory detection in 2014 and 2017. The differences in serum leptin levels between the new hypertensive and non-hypertensive people were compared after three years. The relationship between serum leptin levels and hypertension was analyzed by Logistic regression.. In 2014 and 2017, concentration of serum leptin in females was significantly higher than that in males, and the blood pressure in males was higher than that in females. At the end of follow-up, 26 new cases of hypertension were found. Serum leptin levels were higher in the female hypertensive group than in the non-hypertensive group(P=0. 0289), whereas there was no statistical difference in males(P>0. 01). Regardless of gender, serum leptin was significantly positively correlated with body mass index(BMI) and waist-to-height ratio(WHtR)(P<0. 0001), and also had correlation with blood pressure. However, after adjusting for BMI or WHtR, the correlation between serum leptin and blood pressure disappeared(P>0. 01). Logistic regression also showed the similar result.. Serum leptin is not directly related to blood pressure and hypertension, and the positive correlation between them may be explained largely by BMI and WHtR.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Case-Control Studies; China; Cohort Studies; Female; Follow-Up Studies; Humans; Hypertension; Leptin; Male; Middle Aged; Waist-Height Ratio

Hyperleptinemia is supposed to play a causal role in the development of obesity-associated hypertension, possibly via increased sympathetic tone. Hence patients with congenital leptin deficiency should be hypotensive and their low blood pressure should increase under leptin substitution.. To test this assumption, we examined ambulatory blood pressure, resting heart rate, Schellong test results, cold pressor test results, heart rate variability, catecholamine metabolites, and aldosterone levels in 6 patients with congenital leptin deficiency before as well as 2-7 days and 7-14 months after the start of leptin substitution. Ambulatory blood pressure was also examined in 3 patients with biallelic disease-causing variants in the leptin receptor gene.. Contrary to our expectations, even before leptin substitution, 1 patient with biallelic leptin receptor gene variants and 4 patients with leptin deficiency had been suffering from hypertension. Short-term substitution with leptin increased blood pressure further in 3 out of 4 patients (from 127.0 ± 11.7 to 133.8 ± 10.6 mm Hg), concomitant with an increase in resting heart rate as well as in heart rate during the Schellong test in all patients (from 87.6 ± 7.7 to 99.9 ± 11.0 bpm, p = 0.031, and from 102.9 ± 13.5 to 115.6 ± 11.3 bpm, p = 0.031, respectively). Furthermore, the systolic blood pressure response during the cold pressor test increased in 4 out of 6 patients. Unexpectedly, catecholamine metabolites and aldosterone levels did not increase. After long-term leptin substitution and weight loss, the resting heart rate decreased in 4 out of 6 patients compared to baseline, and in all patients below the heart rate seen immediately after the start of therapy (from 99.9 ± 11.0 to 81.7 ± 5.4 bpm; p = 0.031).. These results show that obesity-associated hypertension does not depend on the presence of leptin. However, short-term leptin substitution can increase the blood pressure and heart rate in obese humans with leptin deficiency, indicating that leptin plays at least an additive role in obesity-associated hypertension. The mechanisms behind this are not clear but might include an increase in regional sympathetic tone.

Topics: Adolescent; Adult; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Child; Cohort Studies; Female; Heart Rate; Hormone Replacement Therapy; Humans; Hypertension; Leptin; Male; Metabolism, Inborn Errors; Obesity; Receptors, Leptin; Weight Loss; Young Adult

We explored the effects of RNA interference-mediated silencing of TLR4 gene on expressions of adipocytokines in obstructive sleep apnea hyponea syndrome (OSAS) with hypertension in a rat model. Systolic blood pressure of caudal artery and physiological changes were observed when establishing rat models of OSAS with hypertension. Mature rat adipocytes were induced from separated and cultured primary rat adipocytes. To transfect rat mature adipocytes, TLR4 siRNA group and negative control (NC) siRNA group were established. Expressions of TLR4 mRNA of adipocytes were examined after silenced by siRNA by quantitative real-time polymerase chain reaction (qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), expressions of inflammatory cytokines, and adipocytokines of adipocytes were detected. Blood pressure in rat caudal artery was higher in the intermittent hypoxia group than that of the blank control group by 29.87 mmHg, and cardiocytes in the former group showed physiological changes, which indicated successful establishment of rat models of OSAS with hypertension. Red particles could be seen in mature rat adipocytes when stained with Oil Red O. Transfection of TLR4 mRNA was significantly suppressed in the TLR4 siRNA group, which didn't happen in the untransfected control group. Rats in the TLR4 siRNA group had significantly reduced expressions of such inflammatory cytokines as interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) and such adipocytokines as visfatin, adiponectin (ADN), and leptin than those in the untransfected control group. RNA interference-mediated silencing of TLR4 gene could regulate occurrence and development of OSAS with hypertension in rats by downregulating expressions of adipocytokines.

Topics: Adipocytes; Adipokines; Adiponectin; Animals; Cytokines; Disease Models, Animal; Gene Expression Regulation; Humans; Hypertension; Interleukin-6; Interleukin-8; Leptin; Male; Nicotinamide Phosphoribosyltransferase; Rats; RNA, Small Interfering; Sleep Apnea, Obstructive; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

The genome-wide association study has founded hypertension-related single nucleotide polymorphism (SNP) rs11191548 near CYP17A1 encoding a key enzyme involved in steroid metabolism, but the molecular mechanisms are not understood and the associations of the SNP with hypertension-related traits are not fully described, especially in children. The aim of the present study is to investigate the associations between the SNP and two hypertension-related traits, lipids and leptin.. We genotyped the SNP in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study. A total of 3503 children participated in the study.. The SNP rs11191548 was significantly associated with high-density lipoprotein cholesterol (HDL) (P = 0.014 and 0.028, respectively) and leptin (P = 0.011 and 0.026, respectively) under an additive model after adjustment for age, gender, and systolic blood pressure (SBP) or diastolic blood pressure (DBP). There was a statistically significant association of rs11191548 with high leptin after adjustment for age, gender, and SBP or DBP. The P-values remain significant after correction for multiple testing.. We demonstrate for the first time that the SNP rs11191548 near CYP17A1 is associated with HDL and leptin in Chinese children. These novel findings provide important evidence that HDL and leptin maybe possibly mediate the process of CYP17A1 involved in hypertension.

Topics: Adolescent; Asian People; Blood Pressure; Child; China; Cholesterol, HDL; Cross-Sectional Studies; Female; Genotyping Techniques; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Polymorphism, Single Nucleotide; Steroid 17-alpha-Hydroxylase

Topics: Animals; Hypertension; Inflammation; Leptin; Male; Obesity; Rats; Rats, Wistar; Saponins; Triterpenes

In the hypothalamic arcuate nucleus (ARC), orexigenic agouti-related peptide (AgRP) neurons regulate feeding behavior and energy homeostasis. The 3-phosphoinositide-dependent protein kinase-1 (PDK1) in AgRP neurons serves as a major signaling molecule for leptin and insulin, the hormones regulating feeding behavior, energy homeostasis and circulation. However, it is unclear whether PDK1 in AGRP neurons is also involved in regulation of blood pressure. This study explored it by generating and analyzing AgRP neuron-specific PDK1 knockout (Agrp-Pdk1

Topics: Agouti-Related Protein; Animals; Arcuate Nucleus of Hypothalamus; Blood Pressure; Calcium-Binding Proteins; Disease Models, Animal; DNA-Binding Proteins; Energy Intake; Feeding Behavior; Gene Expression Regulation; Hypertension; Insulin; Leptin; Mice; Mice, Knockout; Nerve Tissue Proteins; Neurons; Norepinephrine; Nucleobindins; Paraventricular Hypothalamic Nucleus; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; RNA, Messenger; Signal Transduction; Sodium Chloride, Dietary

Apelin and leptin are factors which have a potential physiological and pathological role in cardiovascular homoeostasis. Apelin receptor (APLNR), leptin receptor (LEPR) and leptin variants may affect the vascular tone in heart or peripheral circulation, thereby predisposing patients to hypertension and coronary artery disease (CAD). The aim of the present study was to evaluate four single nucleotide polymorphisms (SNPs) of APLNR genes (rs11544374 and rs948847), LEPR (rs1137101) and leptin (rs7799039) gene in patients with CAD and hypertension.. This case-control study was carried out on 286 CAD-suspected patients. The participants were divided into four subgroups including: CAD patients with no hypertension (H. A significant difference was found in the genotype frequency of APLNR rs11544374 gene in H. The findings of present study revealed that the APLNR rs11544374 gene polymorphism might serve as predisposing factor in CAD.

Topics: Adult; Aged; Alleles; Apelin Receptors; Body Mass Index; Case-Control Studies; Coronary Angiography; Coronary Artery Disease; Female; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Hypertension; Iran; Leptin; Lipid Metabolism; Male; Middle Aged; Odds Ratio; Polymorphism, Single Nucleotide; Receptors, Leptin

Metabolic syndrome (MetS) is associated with osteoporosis due to the underlying inflammatory and hormonal changes. Annatto tocotrienol has been shown to improve medical complications associated with MetS or bone loss in animal studies. This study aimed to investigate the effects of annatto tocotrienol as a single treatment for MetS and osteoporosis in high-carbohydrate high-fat (HCHF) diet-induced MetS animals. Three-month-old male Wistar rats were randomly divided into five groups. The baseline group was euthanized at the onset of the study. The normal group received standard rat chow and tap water. The remaining groups received HCHF diet and treated with three different regimens orally daily: (a) tocopherol-stripped corn oil (the vehicle of tocotrienol), (b) 60 mg/kg annatto tocotrienol, and (c) 100 mg/kg annatto tocotrienol. At the end of the study, measurements of MetS parameters, body compositions, and bone mineral density were performed in animals before sacrifice. Upon euthanasia, blood and femur of the rats were harvested for the evaluations of bone microstructure, biomechanical strength, remodelling activities, hormonal changes, and inflammatory response. Treatment with annatto tocotrienol improved all MetS parameters (except abdominal obesity), trabecular bone microstructure, bone strength, increased osteoclast number, normalized hormonal changes and inflammatory response in the HCHF animals. In conclusion, annatto tocotrienol is a potential agent for managing MetS and osteoporosis concurrently. The beneficial effects of annatto tocotrienol may be attributed to its ability to prevent the hormonal changes and pro-inflammatory state in animals with MetS.

Topics: Adiponectin; Animals; Bixaceae; Bone Resorption; Cancellous Bone; Carotenoids; Diet, High-Fat; Dietary Carbohydrates; Hyperglycemia; Hypertension; Inflammation; Leptin; Male; Metabolic Syndrome; Osteoblasts; Plant Extracts; Rats, Wistar; Tocotrienols; X-Ray Microtomography

Metabolic syndrome (MetS) is widespread among hypertensive patients. Clinical features and potential biomarkers of MetS in the presence of hypertension and resistant hypertension (RHTN) represent a great area of interest for investigation.. The purpose of this study was to evaluate the prevalence of MetS and the clinical features associated with it in resistant and mild to moderate hypertensives.. This cross-sectional study included 236 patients, (i) 129 mild to moderate hypertensive patients and (ii) 107 patients with RHTN. We measured blood pressure (BP) and adipokines levels, and performed bioelectrical impedance analysis. Microalbuminuria (MA), cardiac hypertrophy and arterial stiffness were also assessed. The significance level of alpha = 0.05 was adopted.. We found a MetS prevalence of 73% in resistant and 60% in mild-to-moderate hypertensive patients. In a multiple regression analysis, MA (odds ratio = 8.51; p = 0.01), leptin/adiponectin ratio (LAR) (odds ratio = 4.13; p = 0.01) and RHTN (odds ratio = 3.75; p = 0.03) were independently associated with the presence of MetS apart from potential confounders.. Our findings suggest that both resistant and controlled hypertensive subjects have a high prevalence of MetS. In addition, MetS-related metabolic derangements may cause early renal and hormonal changes. Finally, LAR may be useful as a reliable biomarker for identifying those hypertensive subjects who are at risk for developing MetS.

Topics: Adiponectin; Aged; Antihypertensive Agents; Blood Pressure; Brazil; Cross-Sectional Studies; Echocardiography; Electric Impedance; Female; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Prevalence; Pulse Wave Analysis; Regression Analysis; Risk Factors; Severity of Illness Index; Statistics, Nonparametric

Asian Indians have been shown to have a high prevalence of metabolic syndrome (MetS), related to insulin resistance and possibly genetic factors. The aim of this study was to determine the genetic patterns associated with MetS in Asian Indians living in Durban, South Africa.. Nine hundred and ninety nine participants from the Phoenix Lifestyle Project underwent clinical, biochemical and genetic assessment. MetS was diagnosed according to the harmonized definition. The apolipoprotein A5 Q139X, lipoprotein lipase (LPL) Hinf I, human paraoxonase 1 (PON1) 192Arg/Gln, cholesteryl ester transfer protein (CETP) Taq1B, adiponectin 45T>G and leptin (LEP) 25CAG were genotyped by real-time polymerase chain reaction in participants with and without MetS. Univariate-unadjusted and multivariate-adjusted relations were conducted for all analyses.. The prevalence of MetS was high (49.0%). More females had MetS than males (51.0 vs 42.8%). There was no significant difference in the distribution of genotypes between participants with MetS and those without. Males with the MetS who had the adiponectin TG genotype and human paraoxonase 1 AA genotype were more likely to have reduced high-density lipoprotein cholesterol (HDL-C) (P=0.001) and higher systolic blood pressure (P=0.018), respectively.. About half of the Asian Indians living in Phoenix had MetS. No association between the polymorphisms studied and the risk for MetS was observed. The adiponectin TG genotype may be associated with reduced HDL-C and the human paraoxonase 1 AA genotype with hypertension in males. This suggested that lifestyle factors were the major determinant for MetS in this ethnic group and the genetic risk might be related to its component risk factors than to MetS as an entity.

Topics: Adiponectin; Aged; Apolipoprotein A-V; Aryldialkylphosphatase; Asian People; Cholesterol Ester Transfer Proteins; Cholesterol, HDL; Female; Genetic Association Studies; Humans; Hypertension; Leptin; Lipid Metabolism; Lipoprotein Lipase; Male; Metabolic Syndrome; Middle Aged; Polymorphism, Genetic; Sex Characteristics; South Africa

Continuous nutritional surplus sets the stage for hypertension development. Whereas moderate dietary obesity in mice is normotensive, the homeostatic balance is disrupted concurrent with an increased risk of hypertension. However, it remains unclear how the obesity-associated prehypertensive state is converted into overt hypertension. Here, using mice with high-fat-diet (HFD)-induced moderate obesity vs control diet (CD)-fed lean mice, we comparatively studied the effects of central leptin and tumor necrosis factor-α (TNFα) as well as the involvement of the neuropeptide melanocortin pathway vs the neurotransmitter glutamate pathway. Compared with CD-fed lean mice, the pressor effect of central excess leptin and TNFα, but not melanocortin, was sensitized in HFD-fed mice. The pressor effect of central leptin in HFD-fed mice was strongly suppressed by glutamatergic inhibition but not by melanocortinergic inhibition. The pressor effect of central TNFα was substantially reversed by melanocortinergic inhibition in HFD-fed mice but barely in CD-fed mice. Regardless of diet, the hypertensive effects of central TNFα and melanocortin were both partially reversed by glutamatergic suppression. Hence, neural control of blood pressure is mediated by a signaling network between leptin, TNFα, melanocortin, and glutamate and changes in dynamics due to central excess leptin and TNFα mediate the switch from normal physiology to obesity-related hypertension.

Topics: Animals; Blood Pressure; Brain; Glutamic Acid; Hypertension; Leptin; Male; Melanocortins; Mice; Mice, Inbred C57BL; Neurons; Obesity; Tumor Necrosis Factor-alpha

Protein kinase G (PKG) Iα is the end-effector kinase that mediates nitric oxide (NO)-dependent and oxidant-dependent vasorelaxation to maintain blood pressure during health. A hallmark of cardiovascular disease is attenuated NO production, which in part is caused by NO Synthase (NOS) uncoupling, which in turn increases oxidative stress because of superoxide generation. NOS uncoupling promotes PKG Iα oxidation to the interprotein disulfide state, likely mediated by superoxide-derived hydrogen peroxide, and because the NO-cyclic guanosine monophosphate (cGMP) pathway otherwise negatively regulates oxidation of the kinase to its active disulfide dimeric state. Diet-induced obesity is associated with NOS uncoupling, which may in part contribute to the associated cardiovascular dysfunction due to exacerbated PKG Iα disulfide oxidation to the disulfide state. This is a rational hypothesis because PKG Iα oxidation is known to significantly contribute to heart failure that arises from chronic myocardial oxidative stress.. Bovine arterial endothelial cells (BAECs) or smooth muscle cells (SMCs) were exposed to drugs that uncouple NOS. These included 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) which promotes its S-glutathiolation, 4-diamino-6-hydroxy-pyrimidine (DAHP) which inhibits guanosine-5'-triphosphate-cyclohydrolase 2 to prevent BH. Despite robust evidence for PKG Iα oxidation during NOS uncoupling in cell models, it is unlikely that PKG Iα oxidation occurs to a significant extent in vivo during diet-induced obesity and so is unlikely to mediate the associated cardiovascular dysfunction.

Topics: Animals; Aorta; Carmustine; Cattle; Cyclic GMP-Dependent Protein Kinase Type I; Diet, High-Fat; Endothelial Cells; Gene Expression Regulation; Glucagon; Hypertension; Leptin; Methotrexate; Mice; Myocytes, Smooth Muscle; Nitric Oxide Synthase Type III; Obesity; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species; Resistin; Signal Transduction; Sugar Acids; Uncoupling Agents

Material obesity in rodents is associated with neonatal hyperleptinemia and hypertension of sympathetic origin in adult offspring. Previously, we reported that experimentally induced hyperleptinemia in rat pups results in adulthood hypertension. Here, we addressed the hypothesis that experimental neonatal hyperleptinemia, through renal nerve activation, adversely affects adult renal function.. Sprague-Dawley male and female pups were treated with neonatal leptin (3 mg/kg, intraperitoneal) or neonatal saline, twice daily from postnatal day 9-14. Juvenile (1 month) neonatal leptin and neonatal saline rats were subjected to either bilateral renal denervation, unilateral renal denervation or Sham surgery. Arterial pressure was telemetrically monitored.. Juvenile neonatal leptin rats with intact renal nerves demonstrated increased mean arterial pressure (MAP) accompanied by local renin-angiotensin system overactivity and reduced glomerular filtration rate. Bilateral renal denervation in rats protected against neonatal leptin-induced MAP, renal renin-angiotensin system and impaired glomerular filtration rate. A two-fold increase in sympathetically mediated tubulointerstitial damage in young adult (2 months) neonatal leptin females, was suppressed by unilateral renal denervation, independent of MAP. Neonatal leptin rats also demonstrated increases in urinary protein, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Raised blood pressure was associated with increased salt sensitivity and with sustained renal dysfunction in adulthood.. We propose that neonatal hyperleptinemia programmes long-term renal structural and functional damage, through renal sympathetic nerve activation.

Topics: Animals; Blood Pressure; Denervation; Disease Models, Animal; Female; Hypertension; Kidney; Kidney Diseases; Leptin; Lipocalin-2; Male; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System

The reduction in blood pressure (BP) with continuous positive airway pressure (CPAP) is modest and highly variable. In this study, we identified the variables that predict BP response to CPAP.24-h ambulatory BP monitoring (ABPM), C-reactive protein (CRP), leptin, adiponectin and 24-h urinary catecholamine were measured before and after 6 months of CPAP in obstructive sleep apnoea (OSA) patients.Overall, 88 middle-aged, obese male patients with severe OSA (median apnoea-hypopnoea index 42 events·h

Topics: Blood Pressure; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Catecholamines; Circadian Clocks; Continuous Positive Airway Pressure; Humans; Hypertension; Hypotension; Leptin; Linear Models; Male; Middle Aged; Predictive Value of Tests; Prognosis; Sleep Apnea, Obstructive

The safety of testosterone supplements in men remains unclear. In the present study, we tested the hypothesis that in young and old male spontaneously hypertensive rats (SHR), long-term testosterone supplements increase blood pressure and that the mechanism is mediated in part by activation of the renin-angiotensin system.. In untreated males, serum testosterone exhibited a sustained decrease after 5 months of age, reaching a nadir by 18 to 22 months of age. The reductions in serum testosterone were accompanied by an increase in body weight until very old age (18 months). Testosterone supplements were given for 6 weeks to young (12 weeks-YMSHR) and old (21-22 months-OMSHR) male SHR that increased serum testosterone by 2-fold in young males and by 4-fold in old males. Testosterone supplements decreased body weight, fat mass, lean mass, and plasma leptin, and increased plasma estradiol in YMSHR but had no effect in OMSHR. Mean arterial pressure (MAP) was significantly higher in OMSHR than in YMSHR and testosterone supplements decreased MAP in OMSHR, but significantly increased MAP in YMSHR. Enalapril, the angiotensin-converting enzyme inhibitor, reduced MAP in both control and testosterone-supplemented YMSHR, but had a greater effect on MAP in testosterone-treated rats, suggesting the mechanism responsible for the increase in MAP in YMSHR is mediated at least in part by activation of the renin-angiotensin system.. Taken together with previous studies, these data suggest that testosterone supplements may have differential effects on men depending on age, cardiovascular and metabolic status, and dose and whether given long-term or short-term.

Topics: Adiposity; Age Factors; Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Arterial Pressure; Disease Models, Animal; Enalapril; Estradiol; Hormone Replacement Therapy; Hypertension; Leptin; Male; Rats, Inbred SHR; Renin-Angiotensin System; Risk Factors; Testosterone; Weight Gain

Serum adipokines have a role in the development of arterial stiffness. We aimed to investigate the risk factors of developing arterial stiffness and the association of leptin and arterial stiffness in hypertensive (HTN) patients.. There were 101 HTN patients enrolled. Fasting blood samples and baseline characteristics were obtained and carotid-femoral pulse wave velocity (cfPWV) was measured with the SphygmoCor system. A cfPWV > 10 m/s was defined as high arterial stiffness, and ≤ 10 m/s as low arterial stiffness.. Forty-seven patients (46.5 %) had high arterial stiffness, and had a higher percentage of diabetes (P = 0.044), , older age (P < 0.001), higher pulse pressure (P = 0.049), and higher serum blood urea nitrogen (P = 0.029), creatinine (P = 0.027), intact parathyroid hormone (P = 0.004), serum leptin level (P = 0.002), C-reactive protein (P < 0.001), but lower estimated glomerular filtration rate (P = 0.006) compared to patients with low arterial stiffness. After adjusting for factors significantly associated with arterial stiffness by multivariate logistic regression analysis, it revealed that leptin (aOR = 1.037, 95% CI = 1.007-1.067, P = 0.014), having DM (aOR = 4.885, 95% CI = 1.590-15.006, P = 0.006), and elevated CRP (aOR = 1.503, 95% CI = 1.110-2.0371,P = 0.009) were significant independent predictors of arterial stiffness in HTN patients.. Serum leptin level could be a predictor for arterial stiffness in HTN patients.

Topics: Aged; Biomarkers; Chi-Square Distribution; Cross-Sectional Studies; Female; Humans; Hypertension; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Predictive Value of Tests; Pulse Wave Analysis; Risk Factors; Up-Regulation; Vascular Stiffness

Chemerin is associated with insulin resistance and is expressed in the liver. Nonalcoholic fatty liver disease (NAFLD) is related to impaired insulin sensitivity, but studies evaluating hepatic and serum chemerin in NAFLD resulted in discordant data.. Chemerin mRNA was determined in the liver tissue obtained from 33 controls and 76 NAFLD patients. Chemerin serum levels were measured in a different cohort of patients with ultrasound-diagnosed NAFLD and the respective controls. Hepatic stellate cells and hepatocytes were exposed to selected metabolites and nuclear receptor agonists to study the regulation of chemerin. Effect of recombinant chemerin on hepatocyte released proteins was analysed.. Hepatic chemerin expression was not related to BMI, gender, type 2 diabetes and hypertension. Chemerin mRNA did not correlate with steatosis and was negatively associated with inflammation, fibrosis and nonalcoholic steatohepatitis (NASH) score. Patients with NASH had lower chemerin mRNA compared to those with borderline NASH and controls. Factors with a role in NASH mostly did not regulate chemerin in the liver cells. Of note, liver X receptor agonist reduced chemerin protein. Serum chemerin was not changed in NAFLD. Levels positively correlated with age, waist-to-hip ratio, systolic blood pressure, serum FGF21 and lipocalin 2, and negatively with transferrin saturation. Chemerin induced FGF21 in supernatants of primary human hepatocytes. Hepcidin, a major regulator of iron homoeostasis and lipocalin 2, were not regulated by chemerin.. Chemerin mRNA is reduced in the liver of NASH patients, and liver X receptor seems to have a role herein.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Cell Line; Cells, Cultured; Chemokines; Comorbidity; Cytokines; Diabetes Mellitus, Type 2; Female; Fibroblast Growth Factors; Hep G2 Cells; Hepatic Stellate Cells; Hepatocytes; Hepcidins; Humans; Hydrocarbons, Fluorinated; Hypertension; Hypoglycemic Agents; In Vitro Techniques; Insulin Resistance; Intercellular Signaling Peptides and Proteins; Leptin; Lipocalin-2; Liver; Liver X Receptors; Male; Middle Aged; Non-alcoholic Fatty Liver Disease; Real-Time Polymerase Chain Reaction; Receptors, Cytoplasmic and Nuclear; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Rosiglitazone; Severity of Illness Index; Sulfonamides; Thiazolidinediones; Waist-Hip Ratio; Young Adult

Decreased leptin-induced endothelium-dependent vasodilation has been reported in spontaneously hypertensive rats (SHR). Here, we report leptin-induced vasoconstriction in endothelium-denuded pulmonary artery and thoracic aorta from SHR and sought to characterize calcium handling underlying these mechanisms. Vasoreactivity to leptin was evaluated on pulmonary artery and thoracic aorta rings from 18 weeks old male SHR with or without calcium free medium, caffeine + thapsigargin + carbonyl cyanide-4-trifluoromethoxyphenylhydrazone emptying intracellular calcium stores, nifedipine a voltage-gated calcium channel inhibitor, SKF-96365 a transient receptor potential cation channels (TRPC) inhibitor, wortmaninn, a phosphatidylinositide 3-kinases (PI3K) inhibitor, or PD98059 a mitogen-activated protein kinase kinase (MAPKK) inhibitor. Calcium imaging was performed on cultured vascular smooth muscle cells incubated with leptin in presence or not of wortmaninn or PD98059. Leptin induced vasoconstriction in denuded pulmonary artery and thoracic aorta from SHR. Response was abolished when intra- or extracellular calcium stores were emptied, after blocking TRPC or voltage-dependent calcium channels or when using MAPKK or PI3K inhibitors. In vascular smooth muscle cells, leptin increased intracellular calcium. This rise was higher in SHR and abolished by MAPKK or PI3K inhibitors. TRPC6 gene expression was upregulated in arteries from SHR. Leptin-induced vasoconstriction in denuded arteries of SHR requires intracellular stores and is TRPC- and voltage-gated calcium channels dependent. Intracellular calcium increase is more pronounced in spontaneously hypertensive rats.

Topics: Animals; Aorta, Thoracic; Calcium; Cells, Cultured; Endothelium, Vascular; Hypertension; Leptin; Male; Mitogen-Activated Protein Kinase Kinases; Muscle, Smooth, Vascular; Phosphatidylinositol 3-Kinases; Pulmonary Artery; Rats; Rats, Inbred SHR; Rats, Wistar; Vasoconstriction

The effects of grape-seed polyphenols against the development of hypertension and other cardiometabolic conditions associated with the metabolic syndrome (MetS) were studied in rats fed a high-fat, high-carbohydrate diet, known as the cafeteria (CAF) diet. Two groups of Wistar rats were fed standard (STD) or CAF diets for 12 weeks. The CAF diet-fed rats were administered different doses of a low-molecular-weight grape-seed polyphenol extract (LM-GSPE) (25, 100 and 200 mg/kg per d) or vehicle daily, and the STD diet-fed rats were administered LM-GSPE (100 mg/kg per d) or vehicle using ten animals per group. Body weight (BW), waist perimeter (WP) and systolic and diastolic blood pressures (BP) by the tail-cuff method were recorded weekly. The animals were housed in metabolic chambers every 2 weeks to estimate daily food and liquid intakes and to collect faeces and urine samples. The plasma lipid profile was analysed at time 0 and on the 4th, 7th, 10th and 12th weeks of the experiment. Moreover, plasma leptin was measured at the end of the experiment. Results demonstrated that LM-GSPE, when administered with the CAF diet, attenuated the increase in BP, BW, WP and improved lipid metabolism in these animals. However, although the 25- and 100-mg/kg per d doses were sufficient to produce beneficial effects on BP and lipid metabolism, a 200-mg/kg per d dose was necessary to have an effect on BW and WP. The present findings suggest that LM-GSPE is a good candidate for a BP-lowering agent that can also ameliorate other conditions associated with the MetS.

Topics: Animals; Blood Pressure; Body Weight; Cardiovascular Diseases; Diet; Grape Seed Extract; Hypertension; Leptin; Lipids; Male; Metabolic Syndrome; Phytotherapy; Polyphenols; Rats, Wistar; Risk Factors; Time Factors; Waist Circumference

Modified Lingguizhugan Decoction (MLD) came from famous Chinese medicine Linggui Zhugan Decoction. The MLD is used for the treatment of metabolic syndrome in the clinical setting. Our study focuses on the comprehensive treatment of MLD incorporated with dietary restriction and exercise in a rat model of the metabolic syndrome (MS).. Rats were divided into five groups: control group (Cont), high-fat diet group (HFD), high-fat diet incorporated with dietary restriction group (HFD-DR), exercise incorporated with dietary restriction group (HFD-DR-Ex) and MLD incorporated with dietary restriction and exercise group (HFD-DR-Ex-MLD). Treatments were conducted for 1 week after feeding high-fat diet for 12 weeks. The effects of treatments on high fat diet-induced obesity, hyperglycemia, hyperlipidemia, hypertension, hepatic injury and insulin resistance in rats of MS were examined. In addition, the tumor necrosis factor-α (TNF-α), leptin and protein kinase B (PKB) in rats serum and liver were also examined by enzyme-linked immunosorbent assay (ELISA).. After a week's intervention by dietary restriction, dietary restriction incorporated with exercise or MLD, compared with HFD rats, the relative weight of liver and fat, levels of triglyceride, total cholesterol, low-density lipoprotein, free fatty acid, aspartate aminotransferase, glutamic-pyruvic transaminase and alkaline phosphatase, insulin, were significantly decreased (p < 0.05 or 0.01). This treatment also inhibited abnormal increases of TNF-α, leptin and PKB in serum and liver.. MLD incorporated with dietary restriction and exercise treatment exhibit effects in alleviating high-fat diet-induced obesity, hyperglycemia, hyperlipidemia, hypertension, hepatic injury and insulin resistance, which are possibly due to the down-regulation of TNF-α, leptin and PKB.

Topics: Adipose Tissue; Animals; Blood Pressure; Caloric Restriction; Drugs, Chinese Herbal; Hyperglycemia; Hyperlipidemias; Hypertension; Insulin; Leptin; Lipids; Liver; Magnoliopsida; Male; Metabolic Syndrome; Obesity; Physical Conditioning, Animal; Phytotherapy; Poria; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

During the transition from premenopause to postmenopause, many women experience weight gain and central fat deposition; therefore, we hypothesized that circulating growth factors can play a role in the pathogenesis of hypertension, metabolic syndrome, and subclinical organ damage in perimenopausal women.. The study included 192 women aged 40 to 60years; 152 had newly diagnosed essential hypertension that had never been treated, and 40 were normotensive age-matched controls. For all subjects, 24-h ambulatory blood pressure monitoring (ABPM), echocardiographic examination with assessment of left ventricular mass (LVM) and systolic and diastolic functions (GE Vivid 7.0, General Electric Vingmed Ultrasound, Horten, Norway), carotid ultrasound with measurement of intima-media thickness, and carotid-femoral pulse wave velocity (PWV) measurement (SphygmoCor, AtCor Medical, Sydney, Australia) were performed. Serum levels of insulin-like growth factor 1 (IGF-1), insulin-like growth factor-binding protein 2 (IGFBP-2), and insulin-like growth factor-binding protein 3 (IGFBP-3) were measured using an immunochemical assay.. Hypertensive women had significantly lower IGFBP-2 levels than did normotensive controls (162.9±83.7 vs. 273.1±103.0μg/L, p<0.001); the groups did not differ regarding IGF and IGFBP-3 concentrations. After adjusting the covariates, multivariate analysis showed that IGFBP2 was significantly negatively correlated with 24-h systolic blood pressure (β=-0.31, p=0.02). The adjusted odds ratio for hypertension per standard deviation decrease in IGFBP-2 was 3.43 (95% confidence interval [CI] 1.65-7.13). IGFBP-2 showed a negative correlation with the number of metabolic syndrome components. Independent of body composition, IGFBP-2 was significantly related to left ventricular relative wall thickness and the ratio of mitral inflow velocities as parameter of diastolic function.. In perimenopausal women, decreased IGFBP-2 levels may play a role in blood pressure regulation and the development of subclinical left ventricular diastolic dysfunction. Whether IGFBP-2 is a marker or a mediator of cardiovascular disease in this population merits further investigation.

Topics: Adult; Blood Pressure; Cardiovascular Diseases; Carotid Intima-Media Thickness; Echocardiography; Essential Hypertension; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin-Like Growth Factor Binding Protein 2; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor Binding Proteins; Insulin-Like Growth Factor I; Leptin; Menopause; Metabolic Diseases; Metabolic Syndrome; Middle Aged; Pulse Wave Analysis; Risk Assessment

Insulin receptor substrate 2 (IRS2) is one of the 3 major leptin receptor signaling pathways, but its role in mediating the chronic effects of leptin on blood pressure, food intake, and glucose regulation is unclear. We tested whether genetic inactivation of IRS2 in the entire brain (IRS2/Nestin-cre mice) or specifically in proopiomelanocortin (POMC) neurons (IRS2/POMC-cre mice) attenuates the chronic cardiovascular, metabolic, and antidiabetic effects of leptin. Mice were instrumented with telemetry probes for measurement of blood pressure and heart rate and with venous catheters for intravenous infusions. After a 5-day control period, mice received leptin infusion (2 μg/kg per minute) for 7 days. Compared with control IRS2(flox/flox) mice, IRS2/POMC-cre mice had similar body weight and food intake (33±1 versus 35±1 g and 3.6±0.5 versus 3.8±0.2 g per day) but higher mean arterial pressure (MAP) and heart rate (110±2 versus 102±2 mm Hg and 641±9 versus 616±5 bpm). IRS2/Nestin-cre mice were heavier (38±2 g), slightly hyperphagic (4.5±1.0 g per day), and had higher MAP and heart rate (108±2 mm Hg and 659±9 bpm) compared with control mice. Leptin infusion gradually increased MAP despite decreasing food intake by 31% in IRS2(flox/flox) and in Nestin-cre control mice. In contrast, leptin infusion did not change MAP in IRS2/Nestin-cre or IRS2/POMC-cre mice. The anorexic and antidiabetic effects of leptin, however, were similar in all 3 groups. These results indicate that IRS2 signaling in the central nervous system, and particularly in POMC neurons, is essential for the chronic actions of leptin to raise MAP but not for its anorexic or antidiabetic effects.

Topics: Animals; Appetite; Blood Glucose; Blood Pressure; Disease Models, Animal; Energy Metabolism; Hypertension; Insulin Receptor Substrate Proteins; Leptin; Male; Mice; Mice, Transgenic; Neurons; Pro-Opiomelanocortin; Signal Transduction

Heightened cardiovascular reactivity and delayed recovery to stress are associated with an increased risk of cardiovascular disease. Africans, who are more prone to develop hypertension, show greater cardiovascular reactivity to stress. However, causal factors underlying individual and ethnic differences in stress reactivity and recovery remain largely unexplored. Leptin, which is known for its sympatho-activating effects, is higher in Africans compared to Caucasians for any given body mass index. We compared how cardiovascular reactivity and recovery relate to leptin in African (n = 200) and Caucasian (n = 209) teachers.. We measured leptin in serum and cardiovascular baseline and reactivity continuously with the Finometer device during the cold pressor test for 1 min, and recovery at intervals of 1, 3 and 5 min. Africans had higher body mass index, leptin and blood pressure (all P < 0.001). After full adjustment in multiple regression analyses, associations were seen mainly at the 5 min recovery interval. In Africans, cardiac output reactivity (β = -0.335; P = 0.0018) and arterial compliance- (β = -0.241; P = 0.048) associated negatively and total peripheral resistance- (β = 0.227; P = 0.047) positively with leptin. In Caucasians, diastolic blood pressure correlated positively with leptin (β = 0.200; P = 0.015).. In Africans, higher circulating leptin levels associated with prolonged cardiovascular recovery after exposure to stress which could explain their increased vulnerability to hypertension development.

Topics: Adult; Arterial Pressure; Black People; Body Mass Index; Chi-Square Distribution; Cold Temperature; Cross-Sectional Studies; Female; Health Status; Health Status Disparities; Humans; Hypertension; Leptin; Male; Middle Aged; Multivariate Analysis; Recovery of Function; Risk Factors; South Africa; Stress, Physiological; Time Factors; Vascular Resistance; White People

High-fat diet (HFD)-induced hypertension in rabbits is neurogenic because of the central sympathoexcitatory actions of leptin. Hypothalamic melanocortin and neuropeptide Y (NPY) neurons are recognized as the major signalling pathways through which leptin exerts its central effects. In this study, we assessed the effects of specific antagonists and agonists to melanocortin and NPY receptors on HFD-induced sympathoexcitation and hypertension.. Rabbits were instrumented with intracerebroventricular cannula, renal sympathetic nerve activity (RSNA) electrode, and blood pressure telemetry transmitter.. After 3 weeks HFD (13.5% fat, n = 12) conscious rabbits had higher RSNA (+3.8  nu, P = 0.02), blood pressure (+8.6  mmHg, P < 0.001) and heart rate (+15  b/min, P = 0.01), and brain-derived neurotrophic factor levels in the hypothalamus compared with rabbits fed a control diet (4.2% fat, n = 11). Intracerebroventricular administration of the melanocortin receptor antagonist SHU9119 reduced RSNA (-2.7  nu) and blood pressure (-8.5  mmHg) in HFD but not control rabbits, thus reversing 100% of the hypertension and 70% of the sympathoexcitation induced by a HFD. By contrast, blocking central NPY Y1 receptors with BVD10 increased RSNA only in HFD rabbits. Intracerebroventricular α-melanocortin stimulating hormone increased RSNA and heart rate (P < 0.001) in HFD rabbits but had no effect in control rabbits.. These findings suggest that obesity-induced hypertension and increased RSNA are dependent on the balance between greater activation of melanocortin signalling through melanocortin receptors and lesser activation of NPY sympathoinhibitory signalling. The amplification of the sympathoexcitatory effects of α-melanocortin stimulating hormone also indicates that the underlying mechanism is related to facilitation of leptin-melanocortin signalling, possibly involving chronic activation of brain-derived neurotrophic factor.

Topics: alpha-MSH; Animals; Blood Pressure; Brain-Derived Neurotrophic Factor; Diet, High-Fat; Heart Rate; Hormones; Hypertension; Hypothalamus; Kidney; Leptin; Male; Melanocyte-Stimulating Hormones; Neuropeptide Y; Obesity; Pro-Opiomelanocortin; Rabbits; Receptors, Corticotropin; Receptors, Melanocortin; Receptors, Neuropeptide Y; Sympathetic Nervous System

Obesity is a major risk factor for cardiovascular disease in males and females. Whether obesity triggers cardiovascular disease via similar mechanisms in both the sexes is, however, unknown. In males, the adipokine leptin highly contributes to obesity-related cardiovascular disease by increasing sympathetic activity. Females secrete 3× to 4× more leptin than males, but do not exhibit high sympathetic tone with obesity. Nevertheless, females show inappropriately high aldosterone levels that positively correlate with adiposity and blood pressure (BP). We hypothesized that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in females. Leptin control of the cardiovascular function was analyzed in female mice sensitized to leptin via the deletion of protein tyrosine phosphatase 1b (knockout) and in agouti yellow obese hyperleptinemic mice (Ay). Hypersensitivity to leptin (wild-type, 115 ± 2; protein tyrosine phosphatase 1b knockout, 124 ± 2 mm Hg; P<0.05) and obesity elevated BP (a/a, 113 ± 1; Ay, 128 ± 7 mm Hg; P<0.05) and impaired endothelial function. Chronic leptin receptor antagonism restored BP and endothelial function in protein tyrosine phosphatase 1b knockout and Ay mice. Hypersensitivity to leptin and obesity reduced BP response to ganglionic blockade in both strains and plasma catecholamine levels in protein tyrosine phosphatase 1b knockout mice. Hypersensitivity to leptin and obesity significantly increased plasma aldosterone levels and adrenal CYP11B2 expression. Chronic leptin receptor antagonism reduced aldosterone levels. Furthermore, chronic leptin and mineralocorticoid receptor blockade reduced BP and improved endothelial function in both leptin-sensitized and obese hyperleptinemic female mice. Together, these data demonstrate that leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in female mice and suggest that obesity leads to cardiovascular disease via sex-specific mechanisms.

Topics: Aldosterone; Analysis of Variance; Animals; Cardiovascular Diseases; Disease Models, Animal; Endothelium, Vascular; Female; Hypertension; Leptin; Male; Mice; Mice, Knockout; Mice, Obese; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Random Allocation; Renin-Angiotensin System; Sensitivity and Specificity; Sex Factors; Statistics, Nonparametric

Obesity is characterized by increased circulating levels of the adipocyte-derived hormone leptin, which can increase sympathetic nerve activity and raise blood pressure. A previous study revealed that rats fed a high-fat diet (HFD) have an enhanced hypertensive response to subsequent angiotensin II administration that is mediated at least, in part, by increased activity of brain renin-angiotensin system and proinflammatory cytokines. This study tested whether leptin mediates this HFD-induced sensitization of angiotensin II-elicited hypertension by interacting with brain renin-angiotensin system and proinflammatory cytokine mechanisms. Rats fed an HFD for 3 weeks had significant increases in white adipose tissue mass, plasma leptin levels, and mRNA expression of leptin and its receptors in the lamina terminalis and hypothalamic paraventricular nucleus. Central infusion of a leptin receptor antagonist during HFD feeding abolished HFD sensitization of angiotensin II-elicited hypertension. Furthermore, central infusion of leptin mimicked the sensitizing action of HFD. Concomitant central infusions of the angiotensin II type 1 receptor antagonist irbesartan, the tumor necrosis factor-α synthesis inhibitor pentoxifylline, or the inhibitor of microglial activation minocycline prevented the sensitization produced by central infusion of leptin. RT-PCR analysis indicated that either HFD or leptin administration upregulated mRNA expression of several components of the renin-angiotensin system and proinflammatory cytokines in the lamina terminalis and paraventricular nucleus. The leptin antagonist and the inhibitors of angiotensin II type 1 receptor, tumor necrosis factor-α synthesis, and microglial activation all reversed the expression of these genes. The results suggest that HFD-induced sensitization of angiotensin II-elicited hypertension is mediated by leptin through upregulation of central renin-angiotensin system and proinflammatory cytokines.

Topics: Angiotensin II; Animals; Blood Pressure Determination; Cytokines; Diet, High-Fat; Disease Models, Animal; Hypertension; Inflammation; Leptin; Male; Paraventricular Hypothalamic Nucleus; Random Allocation; Rats; Rats, Sprague-Dawley; Reference Values; Renin-Angiotensin System; RNA, Messenger; Up-Regulation

Neonatal growth restriction (nGR) leads to leptin deficiency and increases the risk of hypertension. Previous studies have shown nGR-related hypertension is normalized by neonatal leptin (nLep) and exacerbated by psychological stress. With recent studies linking leptin and angiotensin signaling, we hypothesized that nGR-induced nLep deficiency increases adult leptin sensitivity; leading to leptin- or stress-induced hypertension, through a pathway involving central angiotensin II type 1 receptors.. We randomized mice with incipient nGR, by virtue of their presence in large litters, to vehicle or physiologic nLep supplementation (80 ng/g/d). Adult caloric intake and arterial pressure were monitored at baseline, during intracerebroventricular losartan infusion and during systemic leptin administration.. nGR increased leptin-triggered renal sympathetic activation and hypertension with increased leptin receptor expression in the arcuate nucleus of the hypothalamus; all of those nGR-associated phenotypes were normalized by nLep. nGR mice also had stress-related hyperphagia and hypertension, but only the stress hypertension was blocked by central losartan infusion.. nGR leads to stress hypertension through a pathway that involves central angiotensin II receptors, and nGR-associated leptin deficiency increases leptin-triggered hypertension in adulthood. These data suggest potential roles for preservation of neonatal growth and nLep supplementation in the prevention of nGR-related hypertension.

Topics: Angiotensins; Animals; Blood Pressure; Disease Models, Animal; Growth Disorders; Hypertension; Leptin; Losartan; Male; Mice; Mice, Inbred C57BL; Random Allocation; Receptors, Angiotensin; Renin-Angiotensin System; Signal Transduction; Stress, Psychological; Sympathetic Nervous System

Consumption of fructose-rich diets in the United States is on the rise and thought to be associated with obesity and cardiometabolic diseases.. We sought to determine the effects of antenatal exposure to high-fructose diet on offspring's development of metabolic syndrome-like phenotype and other cardiovascular disease risk factors later in life.. Pregnant C57BL/6J dams were randomly allocated to fructose solution (10% wt/vol, n = 10) or water (n = 10) as the only drinking fluid from day 1 of pregnancy until delivery. After weaning, pups were started on regular chow, and evaluated at 1 year of life. We measured percent visceral adipose tissue and liver fat infiltrates using computed tomography, and blood pressure using CODA nonivasive monitor. Intraperitoneal glucose tolerance testing with corresponding insulin concentrations were obtained. Serum concentrations of glucose, insulin, triglycerides, total cholesterol, leptin, and adiponectin were measured in duplicate using standardized assays. Fasting homeostatic model assessment was also calculated to assess insulin resistance. P values <.05 were considered statistically significant.. Maternal weight, pup number, and average weight at birth were similar between the 2 groups. Male and female fructose group offspring had higher peak glucose and area under the intraperitoneal glucose tolerance testing curve compared with control, and higher mean arterial pressure compared to control. Female fructose group offspring were heavier and had higher percent visceral adipose tissue, liver fat infiltrates, homeostatic model assessment of insulin resistance scores, insulin area under the intraperitoneal glucose tolerance testing curve, and serum concentrations of leptin, and lower concentrations of adiponectin compared to female control offspring. No significant differences in these parameters were noted in male offspring. Serum concentrations of triglycerides or total cholesterol were not different between the 2 groups for either gender.. Maternal intake of high fructose leads to fetal programming of adult obesity, hypertension, and metabolic dysfunction, all risk factors for cardiovascular disease. This fetal programming is more pronounced in female offspring. Limiting intake of high fructose-enriched diets in pregnancy may have significant impact on long-term health.

Topics: Animals; Blood Glucose; Diet; Fatty Liver; Female; Fructose; Glucose Tolerance Test; Hypertension; Insulin Resistance; Intra-Abdominal Fat; Leptin; Mice, Inbred C57BL; Obesity; Pregnancy; Prenatal Exposure Delayed Effects

To observe mainfestations of syndrome and biochemical indices of hypertensive model rats with excessive accumulation of phlegm-dampness syndrome (EAPDS), and to explore its possible pathological mechanism.. EAPDS rat model was prepared in 50 Wistar rats by feeding with high fat forage. Meanwhile, a normal control group consisting of 10 Wistar rats was set up by feeding with normal forage. After 25-week continuous feeding, 22 rats with body weight (BW) and blood pressure (BP) exceeding 25% those of the control group were selected as a model group. BW, BP, blood lipids, and related serological indicators were detected in all rats. Morphological changes of target organs were observed. mRNA expression levels of leptin receptor (LepR), Janus kinase2 (Jak2), signal transducer and activator of transcription 3 (Stat3), suppressor of cytokine signaling-3 (Socs3), angiotensin II receptor type 1 (AT1), angiotensin II receptor type 2 (AT2), phosphatidylinositol 3 kinase (P13K), serine threonine kinase (Akt), nuclear factor of kappa B (NF-κBp65), inhibitor of nuclear factor kappa-B kinase α (IKKα), NF-kappa-B inhibitor β (lKKβ), NF-kappa-B inhibitor α (IKBα), and AMP-activated protein kinase (AMPK) were detected by quantitative real-time PCR (qPCR). Expression levels of AT1 and LepR in aorta were detected by immunohistochemical assay and Western blot respectively.. Compared with the control group, BW, BP, and blood lipids increased; serum levels of leptin (Lep) , Ang II, Hcy, ET-1, TNF-α, IL-6, and p2-MG increased, but NO decreased in the model group (P < 0.05, P < 0.01). Aortal endothelial injury and smooth muscle cell proliferation occurred in the model group, accompanied with heart and renal injury. Compared with the control group, mRNA expression levels of LepR, Jak2, Stat3, Socs3, AT1 , PI3K, Akt, NF-κB p65, IKKβ, IKBα, and AMPK in aorta were up-regulated significantly (P < 0.05), while the expression of IKKa decreased (P < 0.05). Immunohistochem- ical staining showed, brownish yellow deposit of AT1 and LepR was obviously increased, with more extensively positive distribution. Western blot results showed, as compared with the control group, protein expression levels of AT1 and LepR obviously increased in the model group (P < 0.05).. Model rats exhibited typical syndromes of EAPDS. They put up weight with fat abdomen, gloomy hair, poor appetite, hypersomnia, lowered activities , reduced food intake, loose stool, dark red tongue, white tongue with white, thick, greasy fur. Lep could be taken as one of objective indicators for evaluating hypertension rat model with EAPDS.

Topics: Animals; Aorta; Cell Proliferation; Disease Models, Animal; Hypertension; I-kappa B Proteins; Interleukin-6; Leptin; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphatidylinositol 3-Kinases; Rats; Rats, Wistar; Suppressor of Cytokine Signaling Proteins; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Leptin and TNFα can individually work in the brain to affect blood pressure; however, it remains unknown whether these two cytokines might have an interactive role in this process and, if so, how. In this work, we found that leptin stimulation led to TNFα production under both in vitro and in vivo conditions, and diurnal fluctuation of leptin concentrations in the cerebrospinal fluid predicted the circadian changes of TNFα gene expression in the hypothalamus. Signaling analysis showed that leptin stimulation led to a rapid and strong STAT3 activation followed by a second-phase moderate STAT3 activation, which was selectively abolished by anti-inflammatory chemical PS1145 or TNFα antagonist WP9QY. Physiological study in normal mice revealed that diurnal rise of blood pressure was abrogated following central administration of PS1145 or a leptin receptor antagonist. Central TNFα pretreatment was found to potentiate the effect of leptin in elevating blood pressure in normal mice. In pathophysiology, dietary obesity mimicked TNFα pretreatment in promoting leptin-induced blood pressure rise, and this effect was blocked by central treatment with either PS1145 or WP9QY. Hence, central leptin employs TNFα to mediate the diurnal blood pressure elevation in physiology while enhancement of this mechanism can contribute to hypertension development.

Topics: Animals; Blood Pressure; Circadian Rhythm; HEK293 Cells; Humans; Hypertension; Hypothalamus; In Vitro Techniques; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity; Phosphorylation; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha

Recent studies have demonstrated that epigenetic changes resulting from malnutrition might play important roles in transgenerational links with metabolic diseases. Previously, we observed that exposure to a high-fat diet (HFD) in utero caused a metabolic syndrome-like phenomenon through epigenetic modifications of the adiponectin and leptin genes that persisted for multiple generations. Recent etiological studies indicated that paternal BMI had effects on offspring BMI that were independent of but additive to maternal BMI effects. Thus, we examined whether paternal HFD-induced obesity affected the metabolic status of offspring through epigenetic changes in the adiponectin and leptin genes. Additionally, we investigated whether a normal diet during subsequent generations abolished the epigenetic changes associated with paternal HFD exposure before conception. We observed the effects of paternal HFD exposure before conception over multiple generations on offspring metabolic traits, including weight and fat gain, glucose intolerance, hypertriglyceridemia, abnormal adipocytokine levels, hypertension, and adiponectin and leptin gene expression and epigenetic changes. Normal diet consumption by male offspring during the subsequent generation following paternal HFD exposure diminished whereas consumption for two generations completely abolished the effect of paternal HFD exposure on metabolic traits and adipocytokine promoter epigenetic changes in the offspring. The effects of paternal HFD exposure on offspring were relatively weaker than those following HFD exposure in utero. However, paternal HFD exposure had an additive metabolic effect for two generations, suggesting that both paternal and maternal nutrition might affect offspring metabolism through epigenetic modifications of adipocytokine genes for multiple generations.

Topics: Adipokines; Adiponectin; Animals; Chromatin Immunoprecipitation; Diet, High-Fat; Epigenesis, Genetic; Female; Gene Expression; Glucose Intolerance; Hypertension; Hypertriglyceridemia; Leptin; Male; Metabolic Syndrome; Mice; Obesity; Paternal Exposure; Pregnancy; Prenatal Exposure Delayed Effects; Promoter Regions, Genetic; Real-Time Polymerase Chain Reaction; RNA, Messenger; Weight Gain

We evaluated herein whether diet-induced obesity alters sympathovagal balance, blood pressure, and neuropeptides levels at the hypothalamus and brainstem of mice. Male C57BL6J mice fed with a high-fat (HFD) or a high-fat high-sucrose (HFHSu), or a regular chow diet (C) for 8 weeks were evaluated for metabolic parameters and blood pressure, the latter being performed in conscious freely moving mice. Spectral analysis from the records of systolic blood pressure (SBP) and cardiac pulse intervals (PI) was performed to analyse the autonomic balance in the cardiovascular system. HFD-fed mice developed two distinct hemodynamic phenotypes: hypertensive mice (HFD-H) with high systolic and diastolic BP levels and hypertension-resistant mice (HFD-R) whose BP levels were similar to C group. Spectral analysis of SBP and PI variabilities indicate that the low-frequency (LF)/high-frequency (HF) ratio, which is an index of sympathovagal balance, is higher in HFD-H compared to HFD-R. Along with hypertension and higher LF/HF ratio, HFD-H mice presented increased hypothalamic mRNA levels of cocaine- and amphetamine-regulated transcript (CART), and increased CART-positive neurones in the dorsomedial hypothalamus (DMH) by high-fat diet when compared to C group. Despite developing obesity to similar levels than HFD feeding, intake of a HFHSu was not associated with hypertension in mice neither CART levels increase. Collectively, our main findings indicate that high-fat diet induced-hypertension and autonomic imbalance are associated to an upregulation of CART levels in the DMH of mice.

Topics: Animals; Autonomic Nervous System Diseases; Blood Pressure; Body Weight; Diet, High-Fat; Dorsomedial Hypothalamic Nucleus; Hypertension; Insulin; Interleukin-6; Leptin; Male; Mice; Nerve Tissue Proteins; Obesity; Resistin; Up-Regulation

High fat diet (HFD)-induced hypertension in rabbits is neurogenic and caused by the central action of leptin, which is thought to be dependent on activation of α-melanocortin-stimulating hormone (α-MSH) and neuropeptide Y-positive neurons projecting to the dorsomedial hypothalamus (DMH) and ventromedial hypothalamus (VMH). However, leptin may act directly in these nuclei. Here, we assessed the contribution of leptin, α-MSH, and neuropeptide Y signaling in the DMH and VMH to diet-induced hypertension. Male New Zealand white rabbits were instrumented with a cannula for drug injections into the DMH or VMH and a renal sympathetic nerve activity (RSNA) electrode. After 3 weeks of an HFD (13.3% fat; n=19), rabbits exhibited higher RSNA, mean arterial pressure (MAP), and heart rate compared with control diet-fed animals (4.2% fat; n=15). Intra-VMH injections of a leptin receptor antagonist or SHU9119, a melanocortin 3/4 receptor antagonist, decreased MAP, heart rate, and RSNA compared with vehicle in HFD rabbits (P<0.05) but not in control diet-fed animals. By contrast, α-MSH or neuropeptide Y injected into the VMH had no effect on MAP but produced sympathoexcitation in HFD rabbits (P<0.05) but not in control diet-fed rabbits. The effects of the leptin antagonist, α-MSH, or neuropeptide Y injections into the DMH on MAP or RSNA of HFD rabbits were not different from those after vehicle injection. α-MSH into the DMH of control diet-fed animals did increase MAP, heart rate, and RSNA. We conclude that the VMH is the likely origin of leptin-mediated sympathoexcitation and α-MSH hypersensitivity that contribute to obesity-related hypertension.

Topics: alpha-MSH; Animals; Blood Pressure; Diet, High-Fat; Dorsomedial Hypothalamic Nucleus; Hypertension; Leptin; Male; Melanocyte-Stimulating Hormones; Neuropeptide Y; Obesity; Rabbits; Receptors, Leptin; Receptors, Melanocortin; Signal Transduction; Sympathetic Nervous System; Ventromedial Hypothalamic Nucleus

To investigate the relationship of leptin receptor gene rs1137100 and rs1137101 single nucleotide polymorphrism (SNP) with metabolic syndrome (MS) in older Han adults from major cities in China.. A total of 2082 older Han adults were selected from 18 major cities including 15 provinces/municipalities of China National Nutrition and Health Survey in 2002. According to the MS definition proposed by Joint Interim Statement (JIS), the subjects were divided into MS and control groups. Plasma leptin and insulin levels were measured. The genotypes of rs1137100 and rs1137101 were detected by Taqman method. Association of genotypes of leptin receptor gene SNPs with MS was investigated.. The MS group showed higher body mass index (BMI), waist circumference, fasting serum glucose, systolic blood pressure (SBP) and diastolic blood pressure (DBP), triglycerides (TG), serum total cholesterol (TC), insulin, homeostasis model of assessment for insulin resistence index (HOMA-IR) and leptin levels than those of control individuals, while the high density lipoprotein cholesterol (HDL-c) was significantly lower than the control group. The, GG, AA, GA genotypes distribution and the A allele frequency of rs1137100 and rs1137101 were similar between the two groups. The DBP and SBP level were obviously higher in AA genotype. The HDL-c concentration Was significantly lower in AA and GA + AA genotype. The AA and GA genotypes carriers in rs1137100 had similar risk for MS when comparing with the GG genotypes, and the OR values were 1.23 (95% CI 0.90-1.67) and 2.23 (95% CI 0.83-6.44), respectively. The AA and GA genotypes carriers in rs1137101 had similar risk for MS when comparing with the GG genotypes, and the OR values were 1.23 (95% CI 0.90-1.67) and 2.23 (95% CI 0.83-6.44), respectively.. Leptin receptor genes rs1137100 and rs1137101 are not associated with pathogenesis of MS in older Han adults, but it may relate with hypertension or lipid abnormality.

Topics: Blood Glucose; Blood Pressure; Body Mass Index; Case-Control Studies; China; Cholesterol, HDL; Cities; Gene Frequency; Genotype; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Polymorphism, Single Nucleotide; Receptors, Leptin; Triglycerides; Waist Circumference

Although obesity increases the risk for hypertensive disorders of pregnancy, the mechanisms remain unclear. Neural melanocortin-4 receptor (MC4R) deficiency causes hyperphagia and obesity. Effects of MC4R deficiency on body weight, blood pressure (BP) and placental inflammatory responses to high-fat diet (HFD) are unknown. We tested two hypotheses: MC4R deficiency results in higher body weight, BP and placental inflammation under normal-fat diet (NFD) conditions and HFD exaggerates these responses in MC4R-deficient pregnant rats.. MC4R and MC4R rats were maintained on NFD (13% kcal fat) or HFD (40% kcal fat) for ∼15 weeks, then measurements made on gestational day 19.. MC4R pregnant rats had greater body mass and total body fat and visceral adipose tissue weights along with greater circulating total cholesterol (TC) and leptin levels than MC4R rats regardless of diet. On NFD, circulating adiponectin levels were lower and placental TNFα levels and BP (conscious with carotid catheter) were higher in these heavier rats. Circulating adiponectin levels were lower and placental TNFα levels and BP were higher in MC4R rats compared with NFD controls. These parameters were not affected by HFD in the already heavier and hypertensive MC4R pregnant rats.. Obesity in MC4R deficiency and HFD in MC4R rats result in higher BP and placental inflammation during pregnancy. However, HFD did not exaggerate these responses in already obese MC4R pregnant rats. These data suggest that obesity and HFD are independently related to hypertension and placental inflammation in pregnancy.

Topics: Adiponectin; Adiposity; Animals; Blood Pressure; Body Weight; Cholesterol; Diet, High-Fat; Female; Hypertension; Inflammation; Intra-Abdominal Fat; Leptin; Obesity; Placenta; Pregnancy; Rats; Receptor, Melanocortin, Type 4; Tumor Necrosis Factor-alpha

We previously reported that offspring heterozygous mice partially lacking endothelial nitric oxide synthase (eNOS) gene, and born to hypertensive eNOS-/- Knockout mother, are hypertensive. We hypothesized that those offspring when placed on high-fat diet (HFD) will undergo altered metabolic programming increasing their risk for developing metabolic syndrome.. eNOS-/-KO and wild-type mice (eNOS+/+WT) were cross-bred to produce heterozygous offspring: maternal heterozygous (Mat, eNOS-/+), born from hypertensive eNOS-/-KO mothers; and paternal heterozygous (Pat, eNOS-/+), born from normotensive WT mothers. Mat, eNOS-/+ and Pat, eNOS-/+ female were allocated to HFD or control diet (CD) until 8 weeks of age. Then a metabolic profile was obtained: weight, glucose/insulin tolerance test (GTT, ITT), systolic blood pressure (SBP), serum fasting levels of insulin, adiponectin, leptin, and a lipid panel.. Weight was not different between all offspring within each diet. GTT curve was higher in Mat, eNOS-/+ vs. Pat, eNOS-/+ offspring on both diet (P < 0.001). In ITT, glucose level at 15 minutes was higher in Mat, eNOS-/+ on HFD. Insulin level was increased in Mat, eNOS-/+ vs. Pat, eNOS-/+ on either diet. SBP was elevated in Mat, eNOS-/+ vs. Pat, eNOS-/+ on CD and was further raised in Mat, eNOS-/+ offspring on HFD (P < 0.001). No other differences were seen except for lower high-density lipoprotein levels in Mat, eNOS-/+ fed HFD (P < 0.003).. Mat, eNOS-/+ offspring exposed in utero to maternal hypertension and fed HFD postnatally have increased susceptibility for metabolic abnormalities. Thus, maternal HTN is a risk factor for altered fetal metabolic programming.

Topics: Adiponectin; Animals; Biomarkers; Blood Glucose; Blood Pressure; Diet, High-Fat; Disease Models, Animal; Female; Genetic Predisposition to Disease; Heterozygote; Hypertension; Insulin; Leptin; Lipids; Metabolic Syndrome; Mice, Inbred C57BL; Mice, Knockout; Nitric Oxide Synthase Type III; Phenotype; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Time Factors; Weight Gain

Melanocortin-4 receptor (Mc4r)-expressing neurons in the autonomic nervous system, particularly in the paraventricular nucleus of the hypothalamus (PVH), play an essential role in blood pressure (BP) control. Mc4r-deficient (Mc4rKO) mice are severely obese but lack obesity-related hypertension; they also show a reduced pressor response to salt loading. We have previously reported that lean juvenile offspring born to diet-induced obese rats (OffOb) exhibit sympathetic-mediated hypertension, and we proposed a role for postnatally raised leptin in its etiology. Here, we test the hypothesis that neonatal hyperleptinemia due to maternal obesity induces persistent changes in the central melanocortin system, thereby contributing to offspring hypertension. Working on the OffOb paradigm in both sexes and using transgenic technology to restore Mc4r in the PVH of Mc4rKO (Mc4rPVH) mice, we have now shown that these mice develop higher BP than Mc4rKO or WT mice. We have also found that experimental hyperleptinemia induced in the neonatal period in Mc4rPVH and WT mice, but not in the Mc4rKO mice, leads to heightened BP and severe renal dysfunction. Thus, Mc4r in the PVH appears to be required for early-life programming of hypertension arising from either maternal obesity or neonatal hyperleptinemia. Early-life exposure of the PVH to maternal obesity through postnatal elevation of leptin may have long-term consequences for cardiovascular health.

Topics: Animals; Blood Pressure; Diet; Disease Models, Animal; Female; Humans; Hypertension; Leptin; Male; Maternal-Fetal Relations; Mice, Knockout; Neurons; Obesity; Paraventricular Hypothalamic Nucleus; Pregnancy; Prenatal Exposure Delayed Effects; Receptor, Melanocortin, Type 4; Sympathetic Nervous System

to investigate levels of the stable nitric oxide metabolites (NOx) in hypertensive patients with obesity and hyperleptinemia.. We examined 124 untreated patients (45 men and 79 women) with essential hypertension (EH) (mean age 51.4+/-6.5 years, mean hypertension duration 8.5+/-7.6 years, 64% with visceral obesity) and 25 healthy volunteers (10 men and 15 women with comparable age).. NOx levels were significantly higher in hypertensives (43.18+/-21 mol/l) then in controls (28.3+/-9.6 mol/l; p=0.01). Obese hypertensives had lower NOx concentration than nonobese hypertensives (38.8+/-17.9 and 48.5+/-24.7 mol/l, respectively; <0.05). With increase of degree of obesity NOx levels decreased significantly (r=-0.3; p<0.05). NOx levels correlated with presence (r=-0.44; p<0,05) and degree of obesity (r=-0.3; p<0.05). Hypertensives with high leptin levels had lower NOx concentration (29+/-12.2 mol/l), compared to hypertensives with normal leptin levels (34. 7+/-10.5 mol/l) (p<0.05).

Topics: Aged; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Nitric Oxide; Obesity

The female athlete triad (Triad), links low energy availability (EA), with menstrual dysfunction (MD), and impaired bone health. The aims of this study were to examine associations between EA/MD and energy metabolism and the prevalence of Triad-associated conditions in endurance athletes. Forty women [26.2 ± 5.5 years, body mass index (BMI) 20.6 ± 2.0 kg/m(2), body fat 20.0 ± 3.0%], exercising 11.4 ± 4.5 h/week, were recruited from national teams and competitive clubs. Protocol included gynecological examination; assessment of bone health; indirect respiratory calorimetry; diet and exercise measured 7 days to assess EA; eating disorder (ED) examination; blood analysis. Subjects with low/reduced EA (< 45 kcal/kg FFM/day), had lower resting metabolic rate (RMR) compared with those with optimal EA [28.4 ± 2.0 kcal/kg fat-free mass (FFM)/day vs 30.5 ± 2.2 kcal/kg FFM/day, P < 0.01], as did subjects with MD compared with eumenorrheic subjects (28.6 ± 2.4 kcal/kg FFM/day vs 30.2 ± 1.8 kcal/kg FFM/day, P < 0.05). 63% had low/reduced EA, 25% ED, 60% MD, 45% impaired bone health, and 23% had all three Triad conditions. 53% had low RMR, 25% hypercholesterolemia, and 38% hypoglycemia. Conclusively, athletes with low/reduced EA and/or MD had lowered RMR. Triad-associated conditions were common in this group of athletes, despite a normal BMI range. The high prevalence of ED, MD, and impaired bone health emphasizes the importance of prevention, early detection, and treatment of energy deficiency.

Topics: Adult; Basal Metabolism; Bone Density; Calorimetry, Indirect; Diet Records; Energy Intake; Female; Female Athlete Triad Syndrome; Gynecological Examination; Humans; Hypercholesterolemia; Hypertension; Hypoglycemia; Leptin; Luteinizing Hormone; Menstruation Disturbances; Physical Endurance; Young Adult

Topics: Animals; Hypertension; Leptin; Obesity

Topics: Animals; Hypertension; Leptin; Obesity

We have previously demonstrated that a number of rats fed a moderately high-fat diet (MHFD) become obese and hypertensive and had compromised sympathoinhibitory and vasodilator responses to the gut hormones cholecystokinin (CCK) and gastric leptin. This has implications for increased resistance in vascular beds that attract a large proportion of cardiac output after a meal and may be an important mechanism underlying the development of hypertension in obesity in which food consumption is greatly increased. The aim of this study was to determine whether swapping a MHFD for a low-fat diet (LFD) would induce weight loss in obese animals, reverse the signs of hypertension and restore sympathoinhibitory reflexes. Male Sprague-Dawley rats were placed on a LFD (controls; n = 8) or a MHFD (n = 24) for 11 weeks after which the latter displayed either an obesity-prone (OP) or obesity-resistant (OR) phenotype. All animals were fed a LFD for a further 6 weeks after which they were anaesthetised with isoflurane and artificially ventilated for evaluation of resting arterial pressure (AP) and renal sympathetic nerve responses to CCK (0.1-4 μg/kg) and leptin (15 μg/kg). Weight gain in OP animals remained higher than OR or controls following diet switch (P < 0.05 for both). Resting AP was not significantly different between OP (103 ± 4 mmHg), OR (102 ± 3 mmHg) or control (104 ± 3 mmHg) animals and sympathoinhibitory responses to CCK or leptin were not different between the groups (P > 0.05). These results demonstrate that diet modification can have beneficial effects on sympathetic function and restore normotension without the need for weight reduction.

Topics: Animals; Arterial Pressure; Autonomic Agents; Body Weight; Cholecystokinin; Diet, Fat-Restricted; Diet, High-Fat; Disease Models, Animal; Gastrointestinal Agents; Genetic Predisposition to Disease; Hypertension; Leptin; Male; Obesity; Rats, Sprague-Dawley; Sympathetic Nervous System

Although we previously demonstrated that activation of central nervous system (CNS) melanocortin3/4 receptors (MC3/4R) play a key role in blood pressure (BP) regulation, especially in spontaneously hypertensive rats (SHRs), the importance of hindbrain MC4R is still unclear.. In the present study, we examined the cardiovascular and metabolic effects of chronic inhibition of MC3/4R in the hindbrain of SHRs and normotensive Wistar-Kyoto (WKY) rats. Male WKY rats (n = 6) and SHRs (n = 7) were implanted with telemetry probes to measure BP and heart rate (HR) 24 h/day, and an intracerebroventricular cannula was placed into the fourth ventricle. After 10 days of recovery and 5 days of control measurements, the MC3/4R antagonist (SHU-9119) was infused into the fourth ventricle (1 nmol/h) to antagonize hindbrain MC4R for 10 days, followed by a 5-day recovery period.. Chronic hindbrain MC3/4R antagonism significantly increased food intake and body weight in WKY rats (17 ± 1 to 35 ± 2 g/day and 280 ± 8 to 353 ± 8 g) and SHRs (19 ± 2 to 35 ± 2 g/day and 323 ± 7 to 371 ± 11 g), and markedly increased fasting insulin and leptin levels while causing no changes in blood glucose levels (99 ± 4 to 87 ± 4 and 89 ± 5 to 89 ± 4 mg/dl, respectively, for WKY rats and SHRs). Chronic SHU-9119 infusion reduced mean arterial pressure and HR similarly in WKY rats (-8 ± 1 mmHg and -47 ± 3 b.p.m.) and SHRs (-11 ± 3 mmHg and -44 ± 3 b.p.m.).. These results suggest that although hindbrain MC4R activity contributes to appetite and HR regulation, it does not play a major role in mediating the elevated BP in SHRs.

Topics: Animals; Appetite; Blood Pressure; Body Weight; Eating; Heart Rate; Hypertension; Insulin; Leptin; Male; Melanocyte-Stimulating Hormones; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Rhombencephalon

Despite the fact that obesity is a major risk factor for preeclampsia (PE), the pathophysiological mechanisms whereby obesity and metabolic factors such as leptin increase this risk are unclear. While human data have shown that hyperleptinemia is associated with PE, the long-term effect of hyperleptinemia on blood pressure during pregnancy is unknown. Thus we tested the hypothesis whether chronic circulating leptin elevations in pregnant rats increase blood pressure and placental factors known to play a role in PE. On gestational day (GD)14, rats were assigned to the normal pregnant group with food intake ad libitum (control), leptin-treated (0.5 μg·kg(-1)·min(-1) ip) pregnant group with food intake ad libitum (pregnant+LEP), and normal pregnant group with food intake adjusted to the food intake of pregnant+LEP rats (pregnant-FR). On GD19, mean arterial pressure (MAP) was assessed and tissues were collected. Serum leptin concentration was elevated in pregnant+LEP compared with control and pregnant-FR (18.0 ± 2.8 vs. 0.8 ± 0.1 vs. 0.3 ± 0.1 ng/ml; P < 0.05), which was associated with increased MAP (121.3 ± 8.1 vs. 102.4 ± 2.4 vs. 101.3 ± 1.8 mmHg; P < 0.05). Food intake and body weight were reduced in pregnant+LEP and pregnant-FR by the end of gestation. Additionally, placentas and fetuses of these groups were lighter than those of control. However, placental expression of tumor necrosis factor-α was significantly greater in pregnant+LEP compared with controls (1.6 ± 0.1 vs. 1.1 ± 0.1 pg/mg; P < 0.05). In conclusion, leptin increases blood pressure and placental tumor necrosis factor-α during pregnancy despite its effect of reducing food intake and body weight, and represents a mechanism whereby obesity can promote the development of hypertension in PE.

Topics: Animals; Blood Pressure; Body Weight; Eating; Female; Hypertension; Leptin; Organ Size; Placenta; Pregnancy; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Topics: Animals; Hypertension; Leptin; Obesity

Obesity, a well-known risk factor for developing cardiovascular disease (CVD), is associated with chronic periodontitis in adults. This cross-sectional pilot study on obese adolescents was designed to investigate whether periodontal disease in terms of pathological periodontal pockets is associated with raised blood pressure and other risk markers for CVD.. The study included 75 obese subjects between 12 to 18 years of age, mean 14.5. Subjects answered a questionnaire regarding health, oral hygiene habits and sociodemographic factors. A clinical examination included Visible Plaque Index (VPI %), Gingival inflammation (BOP %) and the occurrence of pathological pockets exceeding 4 mm (PD ≥ 4 mm). Blood serum were collected and analyzed. The systolic and diastolic blood pressures were registered.. Adolescents with pathological periodontal pockets (PD ≥ 4 mm; n = 14) had significantly higher BOP >25% (P = 0.002), higher diastolic blood pressure (P = 0.008), higher levels of Interleukin (IL)-6 (P < 0.001), Leptin (P = 0.018), Macrophage Chemoattractant Protein-1 (MCP-1) (P = 0.049) and thyroid stimulating hormone (TSH) (P = 0.004) in blood serum compared with subjects without pathological periodontal pockets (PD ≥ 4 mm; n = 61). The bivariate linear regression analysis demonstrated that PD ≥ 4 mm (P = 0.008) and systolic blood pressure (P < 0.001) were significantly associated with the dependent variable "diastolic blood pressure". The association between PD ≥ 4 mm and diastolic blood pressure remained significant (P = 0.006) even after adjusting for potential confounders BMI-sds, age, gender, mother's country of birth, BOP >25%, IL-6, IL-8, Leptin, MCP-1, TSH and total cholesterol in the multiple regression analysis.. In conclusion, this study indicates an association between pathological periodontal pockets and diastolic blood pressure in obese adolescents. The association was unaffected by other risk markers for cardiovascular events or periodontal disease. The results call for collaboration between pediatric dentists and medical physicians in preventing obesity development and its associated disorders.

Topics: Adolescent; Age Factors; Body Mass Index; Chemokine CCL2; Child; Cross-Sectional Studies; Dental Plaque Index; Diastole; Female; Humans; Hypertension; Interleukin-6; Interleukin-8; Leptin; Male; Obesity; Periodontal Index; Periodontal Pocket; Pilot Projects; Sex Factors; Systole; Thyrotropin

Hypertension and obesity are known to be linked, with recent studies in mice proposing that leptin may be mediating this effect. This regulation, however, may not extend to humans, where a yet-to-be-identified factor is likely the underlying cause of hypertension.

Topics: Animals; Hypertension; Leptin; Obesity

Hypertension is one of the leading causes of cardiovascular disease (CVD) worldwide. Overweight and obesity are major risk factors for hypertension. The mechanisms linking these two diseases are incompletely understood, but abnormalities in several different pathways including insulin and glucose metabolism, inflammation, the sympathetic nervous system and the renin-angiotensin-aldosterone system have been known for decades. Lately, the attention has shifted toward the endocrine function of adipose tissue, which among others secrete adiponectin, leptin and interleukin-6 (IL-6), which stimulates liver CRP production. These substances have all been regarded as candidate intermediates between adiposity and the development of hypertension. Furthermore, the so-called "natriuretic handicap" which characterizes obesity, has also attracted a great deal of attention as a possible pathway.   Primary hypotheses: • The adipocytokines, adiponectin, leptin and CRP (used as a surrogate marker of IL-6) are independently associated with prevalent and incident hypertension.   • Five-year weight changes associate with BP alterations, even after adjustment for changes in lifestyle risk factors and serum insulin.   • NT-proBNP (used as a surrogate marker of active BNP) is positively associated with prevalent hypertension, but negatively associated with incident hypertension.   • The adipocytokines, adiponectin, leptin and CRP (used as a surrogate marker of IL-6), are independently associated with incident CVD.  . The Inter99 study provided data for this thesis. In brief, Inter99 is a randomized, non-pharmacological intervention study for the prevention of ischemic heart disease. The study included approximately 6,700 participants from the background population, who were thoroughly examined at baseline. Various measurements, including blood samples, were done at baseline and five-year follow-up. Data about cardiovascular events were gathered from national registers.  . Paper I: In the prevalent model including leptin, CRP, adiponectin, sex, age, lifestyle risk factors, lipids, insulin, haemoglobin A1c, and in the incident model which also included baseline heart rate and blood pressure, only leptin of the three candidate intermediates was significantly associated with both prevalent and incident hypertension. Paper II: Five-year weight changes were associated with blood pressure alterations and had a substantial impact on both fasting and two-hour post-glucose serum insulin levels. However, in multivariable regression analyses, additional adjustments for insulin values only attenuated the associations between weight changes and blood pressure minimally. Paper III: Higher serum concentrations of NT-proBNP associated with prevalent hypertension whereas lower concentrations associated with incident hypertension. Paper IV: Among 6,502 participants with a mean follow-up time of 11.4 years, 527 participants experienced one or multiple cardio-vascular events. Among adiponectin, leptin and CRP, only CRP were significantly positive associated with CVD in all models.  . Regarding the pathophysiology of overweight-related hypertension and CVD, our results indicate that:   • Leptin is possibly an independent risk factor for the development of hypertension.   • Albeit weight loss improves insulin-profile, the effect of insulin on blood pressure changes seems minimal, indicating that insulin does not play a major direct role in the early development of hypertension.   • A deficiency of the natriuretic peptides, resulting in reduced vasodilation and natriuresis, could be involved in the pathogenesis of hypertension in its early stages.   • Since adjustment for CRP decreased the BMI-associated CVD risk markedly, our data indirectly suggest that IL-6 originating from fat tissue could play a role in overweight and obesity-related cardiovascular disease.

Topics: Adipokines; Adiponectin; Biomarkers; Blood Pressure; Body Weight; C-Reactive Protein; Cardiovascular Diseases; Humans; Hypertension; Insulin; Interleukin-6; Leptin; Natriuretic Peptides; Obesity; Risk Factors

Protein tyrosine phosphatase 1b (Ptp1b), which represses leptin signaling, is a promising therapeutic target for obesity. Genome wide deletion of Ptp1b, increases leptin sensitivity, protects mice from obesity and diabetes, but alters cardiovascular function by increasing blood pressure (BP). Leptin-control of metabolism is centrally mediated and involves proopiomelanocortin (POMC) neurons. Whether these neurons contribute to leptin-mediated increases in BP remain unclear. We hypothesized that increasing leptin signaling in POMC neurons with Ptp1b deletion will sensitize the cardiovascular system to leptin and enhance neurogenic control of BP. We analyzed the cardiovascular phenotype of Ptp1b+/+ and POMC-Ptp1b-/- mice, at baseline and after 7 days of leptin infusion or sympatho-activation with phenylephrine. POMCPtp1b deletion did not alter baseline cardiovascular hemodynamics (BP, heart rate) but reduced BP response to ganglionic blockade and plasma catecholamine levels that suggests a decreased neurogenic control of BP. In contrast, POMC-Ptp1b deletion increased vascular adrenergic reactivity and aortic α-adrenergic receptors expression. Chronic leptin treatment reduced vascular adrenergic reactivity and blunted diastolic and mean BP increases in POMC-Ptp1b-/- mice only. Similarly POMC-Ptp1b-/- mice exhibited a blunted increased in diastolic and mean BP accompanied by a gradual reduction in adrenergic reactivity in response to chronic vascular sympatho-activation with phenylephrine. Together these data rule out our hypothesis but suggest that deletion of Ptp1b in POMC neurons protects from leptin- and sympatho-mediated increases in BP. Vascular adrenergic desensitization appears as a protective mechanism against hypertension, and POMC-Ptp1b as a key therapeutic target for the treatment of metabolic and cardiovascular dysfunctions associated with obesity.

Topics: Animals; Blood Pressure; Energy Metabolism; Heart Rate; Hypertension; Leptin; Male; Mice; Neurons; Obesity; Phenylephrine; Pro-Opiomelanocortin; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Receptors, Adrenergic, alpha

This study was aimed to investigate the relationship between serum leptin, adiponectin, visfatin levels and obesity and essential hypertension in female subjects.. According to BMI and blood pressure, 206 female participants enrolled were divided into four groups: group 1: obesity and hypertension (48 cases); group 2: non-obesity but hypertension (48 cases); group 3: obesity and normotension (56 cases) and group 4: normal BMI and blood pressure (54 cases). Serum leptin, adiponectin and visfatin levels were detected and their relationships to BMI, blood pressure and waist circumference were analysed.. Serum leptin levels were significantly higher in non-obese groups [group 2: (4.47 ± 1.26) ng/L, group 4: (3.73 ± 1.18) ng/L] than in obese groups [group 1: (2.97 ± 1.46) ng/L, group 3: (3.02 ± 1.18) ng/L], and higher in hypertension groups than in normotension groups. Serum adiponectin levels were obviously higher in group 4 [38.99 (19.75, 103.71) µg/L] than in the other three groups. There were no significant differences in adiponectin levels among group 1, 2 and 3. Serum levels of visfatin were lower in normotension groups [group 3: 3.19 (0.96, 9.45) ng/L; group 4:3.23 (1.92, 4.64) ng/L] than in hypertension groups [group 1: 3.84 (3.40, 5.35) ng/L; group 2: 3.75(1.63, 6.67) ng/L] irrespective of obesity. Logistics regression analysis showed that there was 1.6%, 8.3%, or 5.45% increased risk for hypertension for each 1 µg/L decrease in adiponectin, 1 cm increase in waist circumference, or 1 µg/L increase in visfatin level in obesity, respectively. No relationship could be viewed between leptin and hypertension.. Adiponectin and visfatin levels were correlated with obesity and blood pressure in females. Both adipokines may play a crucial role in the development of hypertension in female obesity.

Topics: Adiponectin; Adult; Blood Pressure; Body Mass Index; Case-Control Studies; Cytokines; Essential Hypertension; Female; Humans; Hypertension; Leptin; Logistic Models; Nicotinamide Phosphoribosyltransferase; Obesity; Risk Factors; Waist Circumference

We compared the obesity parameters and selected adipokines-leptin, adiponectin, and resistin-in obese patients with hypertension and normotensive patients. A total of 67 nondiabetic obese outpatients were divided into 2 groups: A-hypertensive and B-normotensive. Serum levels of leptin, adiponectin, resistin, and insulin were measured. Weight, height, waist circumference, and hip circumference were measured to calculate waist-to-hip ratio (WHR), weight-to-height ratio, visceral adiposity index, and body adiposity index (BAI). Among patients with hypertension, significant positive correlations were observed between leptin and body mass index and BAI (r = .31 and r = .63, respectively). In normotensive patients, leptin positively correlated with BAI (r = .73, P < .01) and negatively with WHR (r = -.55, P < .0001); adiponectin negatively correlated with WHR (r = .38, P < .01) and BAI (r = .52; P < .0001), and resistin negatively correlated with WHR (r = -.36, P < .05). In conclusion, visceral obesity and leptin are associated with hypertension in obese patients.

Topics: Adiponectin; Adiposity; Adult; Biomarkers; Body Mass Index; Case-Control Studies; Female; Humans; Hypertension; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity; Pilot Projects; Predictive Value of Tests; Resistin; Waist Circumference; Waist-Hip Ratio

Leptin and leptin receptor gene polymorphisms have been associated with obesity; however, their association with blood pressure has not been fully elucidated. The aim of this study was to examine the effect of tetranucleotide repeat polymorphism in the 3' flanking region of the leptin and leptin receptor gene on blood pressure in hypertensives with obesity.. Two hundred and eighty hypertensives and 200 healthy controls were analyzed for a tetranucleotide repeat polymorphism of leptin and leptin receptor genes. Genotyping was done by amplifying DNA and determining the allele sizes using gel documentation system. Odds ratios were computed to predict the risk for hypertension caused by specific genotypes of leptin and leptin receptor genes and the effect of interaction between them on the development of hypertension was determined by MDR test.. Significant preponderance in the incidence of male sex, obese individuals and those with positive family history was observed with significant elevation in the mean levels of SBP, DBP, BMI and reduction of HDL levels in hypertensives as compared to controls. Class I/I genotypes of leptin showed significantly high risk for developing hypertension irrespective of obesity. Genotypes of leptin receptor did not confer any risk for hypertension and cohorts studied.. Homozygotes I/I were at greater risk for developing hypertension irrespective of obesity. When leptin and leptin receptor genes were considered together, synergistic interaction was observed between the two genes leading to hypertension, while the polymorphism at leptin gene and obesity was correlated.

Topics: Alleles; Blood Pressure; Case-Control Studies; Female; Genetic Predisposition to Disease; Genotype; Homozygote; Humans; Hypertension; India; Leptin; Male; Microsatellite Repeats; Middle Aged; Obesity; Polymorphism, Genetic; Receptors, Leptin

Vitamin D deficiency and metabolic syndrome are 2 very common health problems in the Spanish population. It has been suggested that patients with metabolic syndrome may be vitamin D deficient more often than subjects without it and that low vitamin D levels may predispose to metabolic syndrome development. However, the results of prospective and intervention studies have been different and such relationship remains unclear. We assessed the relationship between 25-hydroxyvitamin D levels and the prevalence and incidence of metabolic syndrome.. We undertook a population-based cohort study in Spain. At baseline (1996-1998), 1,226 subjects were evaluated. Follow-up visits were performed in 2002-2004 and 2005-2007.At baseline and follow-up, participants underwent an interview and a standardized clinical examination with an oral glucose tolerance test in those subjects without known diabetes. At the second visit, 25-hydroxyvitamin D levels and intact parathyroid hormone levels were measured.. The prevalence of metabolic syndrome at the second and third visit was 29.4 and 42.5%, respectively. Mean levels of 25-hydroxyvitamin D were lower in subjects with metabolic syndrome: 21.7 (6.21) vs 23.35 (6.29) ng/ml, P<.001.The prevalence of vitamin D deficiency (25-hydroxyvitamin D<20 ng/ml) at the second evaluation was 34.7%, with significant differences between subjects with and without metabolic syndrome(34.6 vs 26.5%, P<.01). Men with vitamin D deficiency had more frequently hypertension and metabolic syndrome than men with normal levels. Women with vitamin D deficiency had more frequently hyperglycemia, hypertension, increased waist circumference and hypertriglyceridemia. In a prospective study, 25-hydroxyvitamin D values<20 ng/ml were not significantly associated with an increased risk of developing metabolic syndrome in the next 5 years (odds ratio 0,99, 95% confidence interval 0.57-1.7, P=.97) after adjusting by sex and age.. Vitamin D deficiency is associated with an increased prevalence but not with an increased incidence of metabolic syndrome.

Topics: Adiponectin; Adult; Body Mass Index; Comorbidity; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Hypertension; Hypertriglyceridemia; Interleukin-6; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Prevalence; Prospective Studies; Resistin; Risk Factors; Sex Factors; Tumor Necrosis Factor-alpha; Vitamin D; Vitamin D Deficiency; Waist Circumference

Topics: Adipose Tissue; Animals; Female; Heart; Hypertension; Leptin; Male; Myocardium; Pregnancy; Prenatal Exposure Delayed Effects

Resistant hypertension (RHTN) includes patients with controlled blood pressure (BP) (CRHTN) and uncontrolled BP (UCRHTN). In fact, RHTN patients are more likely to have target organ damage (TOD), and resistin, leptin and adiponectin may affect BP control in these subjects. We assessed the relationship between adipokines levels and arterial stiffness, left ventricular hypertrophy (LVH) and microalbuminuria (MA). This cross-sectional study included CRHTN (n=51) and UCRHTN (n=38) patients for evaluating body mass index, ambulatory blood pressure monitoring, plasma adiponectin, leptin and resistin concentrations, pulse wave velocity (PWV), MA and echocardiography. Leptin and resistin levels were higher in UCRHTN, whereas adiponectin levels were lower in this same subgroup. Similarly, arterial stiffness, LVH and MA were higher in UCRHTN subgroup. Adiponectin levels negatively correlated with PWV (r=-0.42, P<0.01), and MA (r=-0.48, P<0.01) only in UCRHTN. Leptin was positively correlated with PWV (r=0.37, P=0.02) in UCRHTN subgroup, whereas resistin was not correlated with TOD in both subgroups. Adiponectin is associated with arterial stiffness and renal injury in UCRHTN patients, whereas leptin is associated with arterial stiffness in the same subgroup. Taken together, our results showed that those adipokines may contribute to vascular and renal damage in UCRHTN patients.

Topics: Adipokines; Adiponectin; Aged; Albuminuria; Antihypertensive Agents; Biomarkers; Blood Chemical Analysis; Blood Pressure Monitoring, Ambulatory; Body Mass Index; Brazil; Cross-Sectional Studies; Disease Progression; Drug Resistance; Echocardiography, Doppler; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Linear Models; Male; Middle Aged; Multivariate Analysis; Prognosis; Pulse Wave Analysis; Resistin; Statistics, Nonparametric; Vascular Resistance; Vascular Stiffness

In postmenopausal women the mechanisms responsible for hypertension have not been completely elucidated, and there are no gender-specific guidelines for women despite studies showing that blood pressure is not as well controlled to goal in women as in men. In the present study we tested the hypotheses that the sympathetic nervous system and the renal sympathetic nerves contribute to hypertension in aging female rats, that sympathetic activation may be mediated by the melanocortin 3/4 receptor (MC3/4R), and that MC3/4R activation may be due to increases in leptin. α-1, β-1,2-Adrenergic blockade reduced blood pressure in both young (3-4 mo) and old (18-19 mo) female spontaneously hypertensive rats (SHR). Renal denervation attenuated the hypertension more in old females than young females. MC3/4R antagonism with SHU-9119 given intracerebroventricularly had no effect on blood pressure in either young or old females but significantly reduced blood pressure in old males. Plasma leptin levels were similar in old male and female SHR and in old versus young females. These data suggest that the hypertension in old female SHR is in part due to activation of the sympathetic nervous system, that the renal nerves contribute to the hypertension, and that the mechanism responsible for sympathetic activation in old females is independent of the MC3/4R.

Topics: Age Factors; Animals; Blood Pressure; Denervation; Disease Models, Animal; Female; Hypertension; Kidney; Leptin; Melanocyte-Stimulating Hormones; Postmenopause; Rats; Rats, Inbred SHR; Receptor, Melanocortin, Type 2; Receptor, Melanocortin, Type 3; Sympathetic Nervous System

Topics: Adipose Tissue; Animals; Female; Heart; Hypertension; Leptin; Male; Myocardium; Pregnancy; Prenatal Exposure Delayed Effects

Recent research illustrates the role of central melanocortin signaling and leptin in the regulation of arterial blood pressure in animal models. Unraveling the genetic basis of interactions between melanocortin and leptin in humans will provide new insight into the regulation of arterial pressure.. Our study population consisted of 332 Kuwaiti natives. Polymorphisms from exons of leptin, MC3R, and MC4R genes were identified by Sanger sequencing. MC3R expression and leptin levels were determined. Linear regression models, adjusted for age, gender, antihypertensive medication, and body mass index, were used to perform statistical association tests.. We observed a significant association between the MC3R missense variant (rs3827103 [Val81 Ile]) and systolic blood pressure (SBP; P = 0.01, β = 4.9). The N-terminus variant (rs3746619 [Thr6→Lys]) is in linkage disequilibrium (r2 = 0.65) with the rs3827103 variant. The AA haplotype of rs3746619-rs3827103 is significantly associated with SBP (P = 0.005, β=5.03). Minor allele frequencies of these two variants in the Kuwaiti population are twice those seen in European population. In individuals who harbor these variants, we found that the plasma leptin levels were positively correlated with SBP and that the expression of MC3R was downregulated. Leptin levels correlated with obesity traits irrespective of the genotypes at the variant positions.. An increase in leptin levels is known to increase sympathetic nerve activity that, in turn, increases blood pressure. Thus, it is possible that the observed MC3R variants in association with leptin levels are involved in regulation of blood pressure in humans.

Topics: Adult; Asian People; Black People; Blood Pressure; Female; Haplotypes; Humans; Hypertension; Kuwait; Leptin; Male; Middle Aged; Mutation, Missense; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; White People

AT₁ receptor antagonists decrease body weight gain in models of murine obesity. However, fewer data are available concerning the anti-obesity effects of these antagonists, given as a treatment after obesity had been established.. In spontaneously hypertensive rats, obesity was established by cafeteria diet (CD) feeding for 19 weeks. Rats were then were treated with telmisartan (8 mg·kg⁻¹·d⁻¹) or amlodipine (10 mg·kg⁻¹·d⁻¹; serving as blood pressure control) or telmisartan + amlodipine (2 + 10 mg·kg⁻¹·d⁻¹; to control for dose-dependency) for 17 weeks. Rats receiving only chow (C(chow)) or CD-fed rats treated with vehicle (C(CD)) served as controls.. The CD feeding induced obesity, hyperphagia, hyperlipidaemia, and leptin and insulin resistance. Telmisartan reduced the CD-induced increase in body weight and abdominal fat mass. Whereas energy intake was higher rather than lower, the respiratory ratio was lower. After telmisartan, leptin-induced energy intake was reduced and respiratory ratio was increased compared with C(CD) rats. Telmisartan also decreased plasma levels of triglycerides, free fatty acids and low-density lipoprotein. Amlodipine alone or the combination telmisartan + amlodipine did not affect body weight and eating behaviour. Telmisartan, but not amlodipine and telmisartan + amlodipine, improved glucose utilization. The decrease in BP reduction was almost the same in all treatment groups.. Telmisartan exerted anti-obesity effects and restored leptin sensitivity, given as a treatment to rats with obesity. Such effects required high doses of telmisartan and were independent of the decrease in blood pressure.

Topics: Amlodipine; Angiotensin II Type 1 Receptor Blockers; Animals; Anti-Obesity Agents; Antihypertensive Agents; Behavior, Animal; Benzimidazoles; Benzoates; Diet, High-Fat; Dietary Sucrose; Drug Therapy, Combination; Energy Intake; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Random Allocation; Rats; Rats, Inbred SHR; Telmisartan; Weight Gain

Systemic hypertension may be associated with an increased pulmonary vascular resistance, which we hypothesized could be, at least in part, mediated by increased leptin.. Vascular reactivity to phenylephrine (1 μmol/L), endothelin-1 (10 nmol/L) and leptin (0.001-100 nmol/L) was evaluated in endothelium-intact and -denuded isolated thoracic aorta and pulmonary arteries from spontaneously hypertensive versus control Wistar rats. Arteries were sampled for pathobiological evaluation and lung tissue for morphometric evaluation.. In control rats, endothelin-1 induced a higher level of contraction in the pulmonary artery than in the aorta. After phenylephrine or endothelin-1 precontraction, leptin relaxed intact pulmonary artery and aortic rings, while no response was observed in denuded arteries. Spontaneously hypertensive rats presented with increased reactivity to phenylephrine and endothelin-1 in endothelium-intact pulmonary arteries. After endothelin-1 precontraction, endothelium-dependent relaxation to leptin was impaired in pulmonary arteries from hypertensive rats. In both strains of rats, aortic segments were more responsive to leptin than pulmonary artery. In hypertensive rats, pulmonary arteries exhibited increased pulmonary artery medial thickness, associated with increased expressions of preproendothelin-1, endothelin-1 receptors type A and B, inducible nitric oxide synthase and decreased endothelial nitric oxide synthase, together with decreased leptin receptor and increased suppressor of cytokine signaling 3 expressions.. Altered pulmonary vascular reactivity in hypertension may be related to a loss of endothelial buffering of vasoconstriction and decreased leptin-induced vasodilation in conditions of increased endothelin-1.

Topics: Animals; Endothelin-1; Hypertension; Leptin; Male; Organ Culture Techniques; Rats; Rats, Inbred SHR; Rats, Wistar; Vasoconstriction

To study an association of the level of leptin, obesity, and hypertension in a group of ethnic Kyrgyz.. Three hundred and twenty-two Kyrgyz people (145 men and 177 women) who were aged above 30 years and resided in the Kyrgyz Republic were examined. They underwent physical examination involving the collection of complaints and medical history data, objective examination, and anthropometric (height, weight, waist and hip circumference (WC and HC), body mass index (BMI)) and blood pressure (BP) measurements. The persons filled out the Finnish Diabetes Risk Assessment Form including data on vegetable consumption (daily or every other day) and exercise (more or less than 30 min per day). Fasting plasma glucose and serum leptin levels were determined.. All the study participants were allocated to 4 groups according the quartile of leptin levels: < 2.2, 2.2-4.2, 4.3-6.34, and > 6.34 ng/ml for men and < 8.05, 8.05-13.4; 13.5-19.09, and > 19.09 ng/ml for women. The persons in the highest leptin quartile were found to have higher BMI, WC, systolic and diastolic BP (SBP and DBP), and blood glucose levels than those in the lowest quartile. Elevated leptin levels were associated with the higher risk of hypertension. Leptin levels correlated with BMI (r = 0.719; p < 0.001 for men and r = 0.74; p < 0.001 for women) and WC (r = 0.684; p < 0.001 for men; and r = 0.649; p < 0.001 for women). There was also a correlation of leptin levels with SBP (r = 0.355; p < 0.001 and r = 0.277; p < 0.001) and DBP (r = 0.426; p < 0.001 and r = 0.228; p < 0.01) in men and women, respectively.. Leptin levels were associated with obesity and hypertension in the group of ethnic Kyrgyz people.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Body Mass Index; Ethnicity; Female; Humans; Hypertension; Incidence; Kyrgyzstan; Leptin; Male; Middle Aged; Obesity; Prevalence; Retrospective Studies; Risk Assessment; Risk Factors

The adipocytokines, leptin, adiponectin, and interleukin-6, which stimulate liver C-reactive protein (CRP) production, are regarded as potential candidate intermediates between adipose tissue and overweight-induced hypertension.. We examined the associations between leptin, adiponectin, and CRP levels with both prevalent and 5-year incident hypertension (IHT) in a general population of Danish adults (n = 5,868, 51.3% women, mean age 45.8 ± 7.9 years).. We recorded 2195 prevalent and 379 incident cases of hypertension. In models including leptin, CRP, adiponectin, sex, age, lifestyle risk factors, lipids, insulin, hemoglobin A1c, and in the incident model also baseline heart rate and blood pressure, only leptin of the three candidate intermediates was significantly associated with both prevalent and IHT [odds ratio (OR) = 1.18, 95% confidence interval (CI) 1.06-1.32, P = 0.002, and OR = 1.24, 95% CI 1.01-1.54, P = 0.044] for one standard deviation increase in log-transformed leptin levels, respectively. Log-transformed CRP was associated with prevalent (OR = 1.16, 95% CI 1.07-1.26, P < 0.001) but not IHT (OR = 0.98, 95% CI 0.84-1.14, P = 0.76). Log-transformed adiponectin was neither associated with prevalent nor IHT (OR = 0.94, 95% CI 0.87-1.02, P = 0.11 and OR = 0.93, 95% CI 0.80-1.08, P = 0.33). Comparing the lowest with the highest quintile of sex-specific BMI levels, there was an almost two-fold increase in IHT (OR = 1.89, 95% CI 1.10-3.25, P = 0.023) in the fully adjusted model. The population attributable risk estimate of IHT owing to overweight was 31%.. Leptin, but not adiponectin or CRP, may play a mediating role in overweight-induced hypertension. However, as BMI was a strong independent predictor of hypertension, other factors than leptin must be involved in the pathogenesis of overweight-related hypertension.

Topics: Adipokines; Adiponectin; Adult; Body Mass Index; C-Reactive Protein; Denmark; Female; Humans; Hypertension; Incidence; Interleukin-6; Leptin; Male; Middle Aged; Overweight; Prevalence; Prospective Studies; Risk Factors

Metabolic syndrome (MetS) correlates with systemic inflammation. A relation of MetS to periodontitis has been reported. This study aims to evaluate whether periodontitis is associated with untreated MetS, plasma adiponectin, and leptin among Thai people.. One hundred twenty-five participants (aged 35 to 76 years) were recruited. Demographic and biologic data, bleeding on probing (BOP), probing depth (PD), and clinical attachment level (CAL) of all teeth were examined. Plasma adiponectin and leptin levels were measured.. Forty-four participants (35.2%) were healthy, and 81 (64.8%) had MetS. All periodontal conditions (BOP, PD, and CAL) were significantly worse in patients with MetS than healthy participants. After adjustment for confounders, MetS was strongly associated with severe periodontitis (odds ratio [OR] = 3.60, 95% confidence interval [CI]: 1.34 to 9.65). MetS with four to five components had a higher association with periodontitis than did MetS with three components (OR = 5.49, 95% CI: 1.75 to 17.19), whereas each separate component had no association with periodontitis, except for high diastolic blood pressure. Periodontitis was also associated with age (OR = 1.08, 95% CI: 1.01 to 1.14) and education (OR = 3.76, 95% CI: 1.05 to 13.40). The risk of MetS was predicted by body mass index and plasma adiponectin (OR = 1.90, 95% CI: 1.24 to 2.92 and OR = 0.93, 95% CI: 0.88 to 0.98, respectively).. There may be a relationship between untreated MetS and periodontitis in Thai people. Periodontal diagnosis should be regularly conducted in patients with MetS.

Topics: Adiponectin; Adult; Age Factors; Aged; Blood Pressure; Body Mass Index; Diabetes Complications; Educational Status; Female; Humans; Hyperglycemia; Hypertension; Hypertriglyceridemia; Hypoalphalipoproteinemias; Leptin; Male; Metabolic Syndrome; Middle Aged; Periodontal Attachment Loss; Periodontal Index; Periodontal Pocket; Periodontitis; Thailand; Waist Circumference

Weight loss improves insulin sensitivity and exerts sympathomodulatory effects. No data, however, are available on the effects of the weight loss induced by vertical sleeve gastrectomy on sympathetic neural drive, insulin sensitivity, and their reciprocal cross talks. In 10 severe obese hypertensives (age, 54.0±2.3 years [mean±SEM]), we measured sphygmomanometric blood pressure, heart rate, body mass index, homeostatic model assessment index, plasma leptin, muscle sympathetic nerve traffic (microneurography), and baroreflex sensitivity (vasoactive drug technique). Measurements were performed 2 to 3 days before surgery and repeated 6 and 12 months after the procedure. Ten matched hypertensive obeses not undergoing gastrectomy served as controls. Six months after bariatric surgery, a significant (P<0.05) reduction in body mass index (-9.1±1.4 kg/m(2)), sphygmomanometric systolic blood pressure (-10.2±4.5 mm Hg), heart rate (-11.0±2.4 bpm), homeostatic model assessment index (-3-3±1.3 AU), plasma leptin (-53.6±8.8 μg/L), and muscle sympathetic nerve traffic (-15.0±3.4 bursts/100 heart beats) was observed. The weight loss, the plasma leptin reduction, and the sympathetic inhibition were maintained after 12 months, whereas homeostatic model assessment index showed a tendency to return toward presurgery values. A significant improvement in baroreflex control of sympathetic nerve traffic was observed both 6 (+32.1%; P<0.05) and 12 months (+60.7%; P<0.01) after gastrectomy. No significant changes in the above-mentioned variables were detected in the control group. These data provide evidence that massive weight loss induced by sleeve gastrectomy triggers profound sympathoinhibitory effects, associated with a stable and significant reduction in plasma leptin levels, whereas the improvement in insulin sensitivity was attenuated with time and unrelated to the sympathoinhibition.

Topics: Bariatric Surgery; Baroreflex; Blood Pressure; Body Mass Index; Female; Heart Rate; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Sympathetic Nervous System; Treatment Outcome; Weight Loss

The aim of this study was to describe the effect of surgically induced weight loss on vascular function measured by flow-mediated dilatation (FMD) in hypertensive obese patients. This prospective study included 33 patients (78 % females, mean age 53 (9) years) undergoing bariatric surgery (BS). Before and 12 months postoperatively, the BMI, 24-h ambulatory BP, high-sensitivity C-reactive protein (hs-CRP), leptin, homeostasis model assessment (HOMA IR), and abdominal fat were measured. Endothelial function was assessed by FMD. After BS, the excess body weight loss was 71 %; the 24-h [systolic 18(11)//diastolic 7(7) mmHg] BP values, hs-CRP, leptin, HOMA, and abdominal fat significantly decreased, with no changes in endothelial function. Weight loss achieved by BS was associated with a significant improvement in BP and metabolic and inflammation parameters, but FMD did not improve.

Topics: Abdominal Fat; Adult; Bariatric Surgery; Blood Pressure Monitoring, Ambulatory; C-Reactive Protein; Endothelium, Vascular; Female; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Prospective Studies; Treatment Outcome; Vasodilation; Weight Loss

Leptin, an adipocytokine produced by adipose tissue, along with the traditional cardiometabolic risk factors, contributes to the development of cardiovascular complications. At the same time, ethnic features of adipocytokines have been insufficiently investigated, especially among Asians, who have an increased risk of cardiovascular complications compared with Europeans. Aim of study was to investigate the relationship between leptin levels and age, gender, anthropometric parameters, lipid parameters, arterial hypertension (AH), and obesity in the adult population of ethnic Kyrgyz people living in Central Asia.. In total, 322 ethnic Kyrgyz (145 men, 177 women) aged ≥ 30 years were studied. Waist and hip circumference, body mass index, blood glucose, lipids, leptin, and homeostatic model assessment were measured. Patients in the upper quartile of leptin levels had high values of BMI, WC, systolic and diastolic blood pressure, glucose, and HOMA index compared with patients with lower leptin levels. The prevalence of metabolic syndrome and AH increased with higher levels of leptin. Leptin positively correlated with BMI, WC, triglycerides, and glucose concentrations in patients of both sexes. According to the multivariate logistic regression analysis, elevated leptin levels increased by 30 times the risk of obesity in men, regardless of the presence of type 2 diabetes, and 17.7 times in women.. Leptin is associated with general and abdominal obesity, dyslipidemia, and insulin resistance in Kyrgyz patients.

Topics: Adipose Tissue; Adult; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; Diabetes Mellitus, Type 2; Dyslipidemias; Female; Humans; Hypertension; Insulin; Insulin Resistance; Kyrgyzstan; Leptin; Logistic Models; Male; Middle Aged; Obesity; Risk Factors; Triglycerides; Waist Circumference

To measure serum levels of adipsin, leptin, resistin, adiponectin, visfatin, ghrelin and insulin in postmenopausal women screened for the metabolic syndrome (METS).. Serum of 100 postmenopausal women was analyzed using multiplex technology for the mentioned analytes. In addition, values for the homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. Comparisons were performed in accordance to the presence or not of the METS and each of its components. Criteria of the American Heart Association were used to define the METS.. Age and time since menopause onset were similar in women with the METS (n=57) as compared to those without the syndrome (n=43). METS women displayed significantly higher levels of adipsin, leptin, resistin, insulin and HOMA-IR values and lower adiponectin levels. These differences were mainly observed among women with abdominal obesity, independent of fulfilling METS criteria or not. In this same sense, lower adiponectin levels significantly related to low HDL-C and high triglyceride levels; and higher insulin and HOMA-IR values related to high triglyceride and glucose levels, respectively.. In this sample, postmenopausal women with the METS displayed higher insulin and adipokine levels. These were mainly related to abdominal obesity and metabolic and lipid abnormalities. More research is warranted in this regard.

Topics: Adipokines; Adiponectin; Adult; Aged; Blood Glucose; Cholesterol, HDL; Cohort Studies; Complement Factor D; Cytokines; Female; Ghrelin; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Nicotinamide Phosphoribosyltransferase; Obesity, Abdominal; Postmenopause; Resistin; Triglycerides

Topics: Female; Humans; Hypertension; Leptin; Male; Receptor, Melanocortin, Type 3

Topics: Female; Humans; Hypertension; Leptin; Male; Receptor, Melanocortin, Type 3

Obesity is associated with increased blood pressure (BP), which in turn increases the risk of cardiovascular diseases. We found that the increase in leptin levels seen in diet-induced obesity (DIO) drives an increase in BP in rodents, an effect that was not seen in animals deficient in leptin or leptin receptors (LepR). Furthermore, humans with loss-of-function mutations in leptin and the LepR have low BP despite severe obesity. Leptin's effects on BP are mediated by neuronal circuits in the dorsomedial hypothalamus (DMH), as blocking leptin with a specific antibody, antagonist, or inhibition of the activity of LepR-expressing neurons in the DMH caused a rapid reduction of BP in DIO mice, independent of changes in weight. Re-expression of LepRs in the DMH of DIO LepR-deficient mice caused an increase in BP. These studies demonstrate that leptin couples changes in weight to changes in BP in mammalian species.

Topics: Animals; Hypertension; Leptin; Mice, Inbred C57BL; Mutation; Neurons; Obesity; Receptors, Leptin; Signal Transduction

Adipokines are secreted from adipose tissue, influence energy homeostasis and may contribute to the association between obesity and hypertension. Among 1897 participants enrolled in the Multi-Ethnic Study of Atherosclerosis, we examined associations between blood pressure and leptin, tumor necrosis factor-α (TNFα), resistin and total adiponectin. The mean age and body mass index (BMI) was 64.7 years and 28.1, respectively, and 50% were female. After adjustment for risk factors, a 1-s.d.-increment higher leptin level was significantly associated with higher systolic (5.0 mm Hg), diastolic (1.9), mean arterial (2.8) and pulse pressures (3.6), as well as a 34% higher odds for being hypertensive (P<0.01 for all). These associations were not materially different when the other adipokines, as well as BMI, waist circumference or waist-to-hip ratio, were additionally added to the model. Notably, the associations between leptin and hypertension were stronger in men, but were not different by race/ethnic group, BMI or smoking status. Adiponectin, resistin and TNFα were not independently associated with blood pressure or hypertension. Higher serum leptin, but not adiponectin, resistin or TNFα, is associated with higher levels of all measures of blood pressure, as well as a higher odds of hypertension, independent of risk factors, anthropometric measures and other selected adipokines.

Topics: Adiponectin; Adiposity; Aged; Atherosclerosis; Biomarkers; Blood Pressure; Ethnicity; Female; Humans; Hypertension; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Resistin; Risk Factors; Time Factors; Tumor Necrosis Factor-alpha; United States; Up-Regulation

Non-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular atherosclerosis independent of classical risk factors. This study investigated the influence of NAFLD on autonomic changes, which is currently unknown.. Subjects without an overt history of cardiovascular disease were enrolled during health checkups. The subjects diagnosed for NAFLD using ultrasonography underwent 5-min heart rate variability (HRV) measurements that was analyzed using the following indices: (1) the time domain with the standard deviation of N-N (SDNN) intervals and root mean square of successive differences between adjacent N-N intervals (rMSSD); (2) the frequency domain with low frequency (LF) and high frequency (HF) components; and (3) symbolic dynamics analysis. Routine blood biochemistry data and serum leptin levels were analyzed. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured.. Of the 497 subjects (mean age, 46.2 years), 176 (35.4%) had NAFLD. The HRV indices (Ln SDNN, Ln rMSSD, Ln LF, and Ln HF) were significantly decreased in the NAFLD group (3.51 vs 3.62 ms, 3.06 vs 3.22 ms, 5.26 vs 5.49 ms(2), 4.49 vs 5.21 ms(2), respectively, all P<0.05). Ln SDNN was significantly lower in the NAFLD group after adjustment for age, sex, hypertension, dyslipidemia, metabolic syndrome, body mass index, smoking, estimated glomerular filtration rate, HOMA-IR, and leptin (P<0.05). In the symbolic dynamic analysis, 0 V percentage was significantly higher in the NAFLD group (33.8% vs 28.7%, P = 0.001) and significantly correlated with linear HRV indices (Ln SDNN, Ln rMSSD, and Ln HF).. NAFLD is associated with decreased Ln SDNN and increased 0 V percentage. The former association was independent of conventional cardiovascular risk factors and serum biomarkers (insulin resistance and leptin). Further risk stratification of autonomic dysfunction with falls or cardiovascular diseases by these HRV parameters is required in patients with NAFLD.

Topics: Adult; Age Factors; Atherosclerosis; Body Mass Index; Diabetes Mellitus; Fatty Liver; Female; Glomerular Filtration Rate; Heart Rate; Humans; Hypertension; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Middle Aged; Non-alcoholic Fatty Liver Disease; Risk Factors; Sex Factors; Ultrasonography

The prevalence of obesity among pregnant women is increasing. Evidence from human cohort studies and experimental animals suggests that offspring cardiovascular and metabolic function is compromised through early life exposure to maternal obesity. Previously, we reported that juvenile offspring of obese rats develop sympathetically mediated hypertension associated with neonatal hyperleptinemia. We have now addressed the hypothesis that neonatal exposure to raised leptin in the immediate postnatal period plays a causal role. Pups from lean Sprague-Dawley rats were treated either with leptin (3 mg/kg IP) or with saline twice daily from postnatal day 9 to 15 to mimic the exaggerated postnatal leptin surge observed in offspring of obese dams. Cardiovascular function was assessed by radiotelemetry at 30 days, and 2 and 12 months. In juvenile (30 days) leptin-treated rats, hearts were heavier and night-time (active period) systolic blood pressure was raised (mm Hg; mean ± SEM: male leptin-treated, 132 ± 1 versus saline-treated, 119 ± 1, n=6, P<0.05; female leptin-treated, 132 ± 2 versus saline-treated, 119 ± 1, n=6, P<0.01), and the pressor response to restraint stress and leptin challenge increased compared with saline-treated rats. Heart rate variability demonstrated an increased low:high frequency ratio in 30-day leptin-treated animals, indicative of heightened sympathetic efferent tone. Echocardiography showed altered left ventricular structure and systolic function in 30-day female leptin versus saline-treated rats. These disorders persisted to adulthood. In isolated hearts, contractile function was impaired at 5 months in male leptin-treated rats. Exogenously imposed hyperleptinemia in neonatal rats permanently influences blood pressure and cardiac structure and function.

Topics: Adipose Tissue; Animals; Animals, Newborn; Blood Pressure; Body Weight; Cardiovascular System; Female; Heart; Heart Rate; Hypertension; Leptin; Male; Myocardial Contraction; Myocardium; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley

Although pregnancies associated with hyperinsulinemia and altered placental angiogenic and inflammatory factors are at increased risk for developing preeclampsia, the effects of euglycemic hyperinsulinemia on placental factors and blood pressure regulation during pregnancy are unclear. We hypothesized that chronic hyperinsulinemia results in increased placental soluble fms-like tyrosine kinase 1(sFlt-1) and tumor necrosis factor α (TNF- α) levels and hypertension in pregnant rats.. On gestational day (GD) 14, Sprague-Dawley rats were assigned as normal pregnant or pregnant + insulin. Insulin was infused subcutaneously by osmotic minipump for 5 days at a dose of 1.5 mU/kg/min. Those rats receiving insulin were supplemented with 20% glucose in drinking water to maintain euglycemia. On GD 19, mean arterial pressure (MAP) and heart rate (HR) were assessed in conscious rats by indwelling carotid catheters, followed by collections of blood, placentas, and fetuses. In addition to placental sFlt-1 and TNF-α levels, circulating insulin, glucose, leptin, cholesterol, triglyceride, and free fatty acid concentrations were measured.. MAP was higher in pregnant + insulin vs. normal pregnant rats; however, HR was similar between groups. Although litter size and placental weight were comparable, fetuses from pregnant + insulin rats were heavier. Importantly, circulating insulin concentration was elevated in the pregnant + insulin group, with no change in glucose level. Moreover, circulating leptin, cholesterol, triglyceride, and free fatty acid concentrations were increased in the pregnant + insulin group. There were no differences in placental sFlt-1 and TNF-α concentrations between groups.. In summary, sustained euglycemic hyperinsulinemia, comparable with insulin levels in preeclamptic women, can raise blood pressure in pregnancy independent of recognized placental factors associated with preeclampsia.

Topics: Animals; Biomarkers; Blood Pressure; Cholesterol; Disease Models, Animal; Female; Glucose; Heart Rate; Hyperinsulinism; Hypertension; Insulin; Leptin; Placenta; Pre-Eclampsia; Pregnancy; Random Allocation; Rats; Rats, Sprague-Dawley; Triglycerides; Tumor Necrosis Factor-alpha; Vascular Endothelial Growth Factor Receptor-1

Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with HTN in RA.. We compared measures of inflammation [serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), homocysteine, and leptin concentrations] and insulin resistance [homeostasis model assessment index (HOMA)] in RA patients with (n = 90) and without HTN (n = 79). HTN was defined as blood pressure ≥ 140/90 mm Hg or treatment with antihypertensive therapy. The independent association of markers of interest with HTN was examined using multivariable logistic regression.. Patients with HTN were significantly older and had longer disease duration than those without HTN (both p < 0.001). Concentrations of homocysteine [11.1 (8.5-13.5) μmol/l vs 9.3 (7.8-11.0) μmol/l] were significantly higher in patients with HTN (p < 0.001). After adjustment for age, sex, race, smoking, body mass index, and corticosteroid and nonsteroidal antiinflammatory drugs (NSAID) use, increased concentrations of homocysteine (OR 2.9, 95% CI: 1.5-5.5, p = 0.001), and leptin (OR 2.0, 95% CI: 1.0-3.8, p = 0.046) were significantly associated with HTN, but the 28-joint Disease Activity Score, IL-6, CRP, TNF-α, and HOMA index were not (all p > 0.05).. HTN in patients with RA is not associated with generalized systemic inflammation or insulin resistance, but is associated with increasing concentrations of homocysteine and leptin. The pathogenesis of HTN in RA may involve pathways more regularly associated with fat and vascular homeostasis.

Topics: Adult; Aged; Arthritis, Rheumatoid; Biomarkers; C-Reactive Protein; Female; Humans; Hypertension; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Male; Middle Aged; Risk Factors; Tumor Necrosis Factor-alpha

Insulin resistance, dyslipidemia and hypertension are independent mediators of endothelial dysfunction. It is incompletely defined whether dyslipidemia and hypertension in addition to diabetes mellitus type II (DMII), as seen in the metabolic syndrome (MS), worsen diabetes-induced endothelial dysfunction. Furthermore, it is unclear whether treatment influences endothelial dysfunction similarly in MS and DMII. Therefore, we studied vascular reactivity and the effect of in vivo treatment with angiotensin-converting enzyme inhibition (ACE-I) or hypocaloric diet in LDL receptor- and leptin-deficient (ob/ob), double knockout mice (DKO), featuring MS and in ob/ob mice with DMII.. Vascular reactivity was studied in isolated aortic ring segments. Maximum vasorelaxant response to acetylcholine (Ach) was more depressed in DKO than in ob/ob mice, whereas response to bradykinin (BK) was equally attenuated in both genotypes (52 ± 3 and 23 ± 9% reversal of preconstriction induced by 10(-7) M phenylephrine in DKO vs. 76 ± 3 and 23 ± 8% reversal of preconstriction in ob/ob mice, respectively). ACE-I and hypocaloric diet improved ACh-induced vasorelaxation significantly (89 ± 2 and 59 ± 2% reversal of preconstriction in DKO vs. 80 ± 3 and 84 ± 4% in ob/ob mice, respectively), but not the response to BK.. These results indicate a differential impact of DMII and MS on endothelial function. ACE-I and hypocaloric diet improved ACh-, but not BK-induced vasorelaxation in these mouse models of DMII and MS.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Biomarkers; Blood Glucose; Caloric Restriction; Captopril; Combined Modality Therapy; Diabetes Mellitus, Type 2; Disease Models, Animal; Dose-Response Relationship, Drug; Dyslipidemias; Endothelium, Vascular; Female; Hypertension; Leptin; Lipids; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Nitric Oxide; Receptors, LDL; Time Factors; Vasodilation; Vasodilator Agents; Weight Loss

Leptin and aldosterone have been associated with the pathophysiological mechanisms of hypertension. However, despite studies showing the association of leptin with intima-media thickness, arterial distensibility and sympathetic nerve activation, the relationship between leptin and blood pressure (BP) in resistant hypertension (RHTN) is unknown. We aimed to assess the correlation of plasma leptin and aldosterone levels with BP in uncontrolled controlled RHTN (UCRHTN) and CRHTN patients. Plasma leptin and aldosterone levels, office BP, ambulatory BP monitoring and heart rate were measured in 41 UCRHTN, 39 CRHTN and 31 well-controlled HTN patients. No differences were observed between the three groups regarding gender, body mass index and age. The UCRHTN group had increased leptin when compared with CRHTN and well-controlled HTN patients (38.2±21.4, 19.6±8.7 and 20.94±13.9 ng ml(-1), respectively; P<0.05). Aldosterone levels values were also statistically different when comparing RHTN, CRHTN and well-controlled HTN patients (9.6±3.8, 8.1±5.0 and 8.0±4.7 ng dl(-1), respectively; P<0.05). As expected, UCRHTN patients had higher heart rate values compared with CRHTN and well-controlled HTN patients (86.2±7.2, 83.5±6.7 and 83.4±8.5, respectively; P<0.05). Plasma leptin positively correlated with systolic (SBP) and diastolic BP (DBP), and aldosterone (r=0.43, 0.35 and 0.47, respectively; all P<0.05) in UCRHTN, but neither in the CRHTN nor in the HTN group. Simple linear regression showed that SBP, DBP and aldosterone may be predicted by leptin (r(2)=0.16, 0.15 and 0.19, respectively; all P<0.05) only in the UCRHTN subgroup. In conclusion, UCRHTN patients have higher circulating leptin levels associated with increased plasma aldosterone and BP levels when compared with CRHTN and HTN subjects.

Topics: Aged; Aldosterone; Antihypertensive Agents; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Drug Resistance; Female; Heart Rate; Humans; Hypertension; Leptin; Linear Models; Male; Middle Aged; Predictive Value of Tests; Risk Factors; Treatment Failure; Up-Regulation

Epidemiological data in humans and experiments in laboratory animals have demonstrated that the developmental programming of hypertension may occur as a consequence of dietary manipulations during pregnancy. Surprisingly, there is a scarcity of data regarding the development of hypertension as a consequence of a maternal low-protein diet (MLPD), particularly in the mouse. Furthermore, the role of sex in developmental programming is not well understood. We used FVB/NJ mice, because of their value in genetic/mechanistic analysis, to test the hypothesis that a MLPD during gestation leads to the sexually dimorphic developmental programming of hypertension and related disorders, such as intra-uterine growth restriction (IUGR), type 2 diabetes mellitus and obesity. We administered iso-caloric, normal (control), moderate protein (moderate MLPD) and severe protein (severe MLPD) diets to the mice, beginning 1 week before mating and continuing until the delivery of the pups. From 4 weeks onward, using a non-invasive tail-cuff method, we measured blood pressure and other parameters in the offspring. Our results demonstrate the following: (1) MLPD caused IUGR (low birthweight) in a dose-dependent manner; (2) Female offspring developed severe hypertension, whereas males were affected only moderately; (3) The blood glucose level was elevated only in females from the moderate MLPD group, although their insulin levels remained normal; (4) Rapid catch-up growth was observed in both sexes, with moderate MLPD females and severe MLPD males becoming overweight. Notably, blood leptin levels in the control group were significantly higher in females than in male offspring and were reduced in females from the severe MLPD group. We conclude that an antenatal MLPD during gestation leads to sexually dimorphic programming in mice.

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Diabetes Mellitus, Type 2; Diet, Protein-Restricted; Dietary Proteins; Female; Fetal Growth Retardation; Heart Rate; Hypertension; Insulin; Leptin; Male; Mice; Mice, Inbred Strains; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Sex Characteristics

To assess whether sleep apnea severity has an independent relationship with leptin levels in blood after adjusting for different measures of obesity and whether the relationship between obstructive sleep apnea (OSA) severity and leptin levels differs depending on obesity level.. Cross-sectional study of 452 untreated OSA patients (377 males and 75 females), in the Icelandic Sleep Apnea Cohort (ISAC), age 54.3±10.6 (mean±s.d.), body mass index (BMI) 32.7±5.3 kg m(-2) and apnea-hypopnea index 40.2±16.1 events per h. A sleep study and magnetic resonance imaging of abdominal visceral and subcutaneous fat volume were performed, as well as fasting serum morning leptin levels were measured.. Leptin levels were more highly correlated with BMI, total abdominal and subcutaneous fat volume than visceral fat volume per se. No relationship was found between sleep apnea severity and leptin levels, assessed within three BMI groups (BMI <30, BMI 30-35 and BMI > or =35 kg m(-2)). In a multiple linear regression model, adjusted for gender, BMI explained 38.7% of the variance in leptin levels, gender explained 21.2% but OSA severity did not have a significant role and no interaction was found between OSA severity and BMI on leptin levels. However, hypertension had a significant effect on the interaction between OSA severity and obesity (P=0.04). In post-hoc analysis for nonhypertensive OSA subjects (n=249), the association between leptin levels and OSA severity explained a minor but significant variance (3.2%) in leptin levels. This relationship was greatest for nonobese nonhypertensive subjects (significant interaction with obesity level). No relationship of OSA severity and leptin levels was found for hypertensive subjects (n=199).. Obesity and gender are the dominant determinants of leptin levels. OSA severity is not related to leptin levels except to a minor degree in nonhypertensive nonobese OSA subjects.

Topics: Adult; Biomarkers; Body Composition; Body Mass Index; Cohort Studies; Cross-Sectional Studies; Female; Humans; Hypertension; Iceland; Intra-Abdominal Fat; Leptin; Male; Middle Aged; Obesity; Polysomnography; Severity of Illness Index; Sex Distribution; Sleep Apnea Syndromes; Subcutaneous Fat; Surveys and Questionnaires; Time Factors

Obesity is characterized by hyperleptinaemia, which is associated with diabetes, hypertension and coronary heart disease. The aim of this study was to determine if body fat and muscle measures predict the natural increase in leptin over 2·6 years in older adults.. A total of 190 subjects (50% females) aged between 50 and 79 years were selected to perform the serum measurements for leptin. Height and weight were measured and body mass index (BMI) was calculated. Fat and lean mass of the whole body and the trunk were acquired through dual-energy X-ray absorptiometry (DXA). Leg muscle strength and handgrip strength were measured using dynamometry.. In multivariable analyses, leg muscle strength was negatively associated with both baseline leptin (β: -0·05 μg/l per kg, 95% CI: -0·08, -0·02) and follow-up leptin (β: -0·04 μg/l per kg, 95% CI: -0·07, -0·01). BMI, and percentage total fat and trunk fat and their respective change per annum (cpa) were significantly and positively associated with leptin. Lean mass was negatively associated with baseline leptin. Gender-specific analyses produced similar associations between leg muscle strength, fat measures and follow-up leptin in males and females.. Besides positive associations between body fat, trunk fat and leptin, we found that leg muscle strength was negatively associated with leptin after 2·6 years in a sample of older population. This suggests that interventions to maintain or increase muscle strength may have a protective effect on hyperleptinaemia.

Topics: Absorptiometry, Photon; Adipose Tissue; Aged; Aged, 80 and over; Body Mass Index; Coronary Disease; Female; Hand Strength; Humans; Hypertension; Leptin; Male; Middle Aged; Muscle Strength

Obesity induced by Western diets is associated with type 2 diabetes mellitus and cardiovascular diseases, although underlying mechanisms are unclear. We investigated a murine model of diet-induced obesity to determine the effect of transient potential receptor vanilloid 1 (TRPV1) deletion on hypertension and metabolic syndrome. Wild-type and TRPV1 knockout mice were fed normal or high-fat diet from 3 to 15 weeks. High-fat diet-fed mice from both genotypes became obese, with similar increases in body and adipose tissue weights. High-fat diet-fed TRPV1 knockout mice showed significantly improved handling of glucose compared with high-fat diet-fed wild-type mice. Hypertension, vascular hypertrophy, and altered nociception were observed in high-fat diet-fed wild-type but not high-fat diet-fed TRPV1 knockout mice. Wild-type, but not high-fat diet-fed TRPV1 knockout, mice demonstrated remodeling in terms of aortic vascular hypertrophy and increased heart and kidney weight, although resistance vessel responses were similar in each. Moreover, the wild-type mice had significantly increased plasma levels of leptin, interleukin 10 and interleukin 1β, whereas samples from TRPV1 knockout mice did not show significant increases. Our results do not support the concept that TRPV1 plays a major role in influencing weight gain. However, we identified a role of TRPV1 in the deleterious effects observed with high-fat feeding in terms of inducing hypertension, impairing thermal nociception sensitivity, and reducing glucose tolerance. The observation of raised levels of adipokines in wild-type but not TRPV1 knockout mice is in keeping with TRPV1 involvement in stimulating the proinflammatory network that is central to obesity-induced hypertension and sensory neuronal dysfunction.

Topics: Adipose Tissue; Animals; Blood Glucose; Blood Pressure; Cardiovascular Diseases; Diet, High-Fat; Hypertension; Insulin Resistance; Interleukin-10; Interleukin-1beta; Leptin; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; TRPV Cation Channels

Feeding a high-fat diet (HFD) to rabbits results in increased blood pressure and renal sympathetic nerve activity (RSNA) and marked increases in plasma leptin and insulin. We determined the contribution of insulin and leptin signaling in the central nervous system to the increased blood pressure and RSNA during a HFD using specific antagonists. New Zealand White rabbits were implanted with an intracerebroventricular (ICV) catheter and RSNA electrode and placed on a normal or 13.5% HFD for 1 or 3 weeks. Blood pressure, heart rate, and RSNA were recorded before and for 90 minutes after ICV administration of a leptin antagonist (100 µg), insulin antagonist (0.5 U), or vehicle (50 µL) on separate days. Rabbits had higher blood pressure (+8%, +17%) and RSNA (+55%, +71%), at 1 and 3 weeks, respectively, of HFD compared with controls (n=7-11). ICV leptin antagonist reduced blood pressure by 9% and RSNA by 17% (P<0.001) after 3 weeks of HFD but had no effect at week 1. ICV administration of the insulin antagonist reduced blood pressure by ≈5% at both times (P<0.05) but there was no effect on RSNA. Leptin and insulin antagonist doses were confirmed to effectively block the pressor responses to ICV leptin and insulin, respectively. The elevation of blood pressure and RSNA induced by a HFD is predominantly mediated by central actions of leptin. Central actions of insulin contribute a smaller proportion of the hypertension but independently of RSNA.

Topics: Animals; Antihypertensive Agents; Blood Pressure; Diet, High-Fat; Heart Rate; Hypertension; Insulin; Insulin Antagonists; Kidney; Leptin; Male; Obesity; Rabbits; Signal Transduction; Sympathetic Nervous System

High blood pressure, in relation to blood levels of adipokines such as adiponectin and leptin, is highly associated with an unhealthy lifestyle including sedentary behaviors, poor dietary habits such as excess sodium intake, and heavy drinking. Strategies to reduce blood pressure may benefit the levels of adipokines.. Thus, we aimed to investigate the effects of lifestyle intervention on blood pressure and serum adipokines in middle-aged Korean men with borderline high blood pressure (systolic blood pressure [SBP] ≥ 130 mm Hg or diastolic blood pressure [DBP] ≥ 85 mm Hg).. Fifty-two men (aged 42.5 ± 8.5 years) with normal weight (body mass index [BMI] < 25 kg/m(2)) and high BP (NH group) and 40 men (age 42.0 ± 8.4 years) who were obese (BMI ≥ 25 kg/m(2)) with high BP (OH group) underwent 5 sessions of one-on-one intensive counseling including instruction on a nutritionally balanced diet, a low-sodium diet, how to understand calorie requirements, and strategies to implement regular exercise for blood pressure regulation over 12 weeks. In order to increase the awareness of sodium education, a salt sensory test using an unseasoned soup was performed. Anthropometrics, blood pressure measurements, 24-hour recalls were performed, and blood levels of lipids, fasting plasma glucose, C-reactive protein (CRP), leptin, and adiponectin were analyzed at week 0 and at week 12. Sodium consumption was roughly estimated using the Dish-based Frequency Questionnaire-15.. Weight, BMI, body fat (kg and %), waist circumference, hip circumference, and blood pressure were significantly decreased after 12 weeks (p < 0.05) in all subjects. Similarly, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and CRP were decreased (p < 0.05), but LDL-C/HDL-C was significantly decreased (p < 0.01) only in the obese subjects. At baseline, blood levels of leptin were significantly higher in the obese subjects than in the normal weight subjects. In the obese subjects, a significantly negative correlation was found between leptin levels at baseline and percentage change in DBP (r = -0.338, p < 0.05). After 12 weeks, blood levels of adipokines did not show significant changes.. These results suggest that a short-term (12 weeks) lifestyle intervention had positive effects on blood pressure control and weight reduction in the subjects, but not on their blood levels of adipokines. It is interesting that blood level of baseline leptin was negatively associated with the changes in blood pressure after this short-term intervention.

Topics: Adipokines; Adipose Tissue; Adult; Asian People; Blood Glucose; Blood Pressure; Body Mass Index; C-Reactive Protein; Cholesterol, HDL; Cholesterol, LDL; Diet, Sodium-Restricted; Exercise; Fasting; Humans; Hypertension; Leptin; Life Style; Male; Middle Aged; Obesity; Surveys and Questionnaires; Weight Loss

Previous research has demonstrated that adipokines influence blood pressure (BP). Limited data exist in healthy adolescents, who are in a critical period for preventing the development of high BP. This study investigated the association of leptin, adiponectin and the leptin-to-adiponectin ratio (LAR) with BP in rural Chinese adolescents. This report included 1245 adolescents (average body mass index: 19.3 kg m(-2)) aged 13-21 years from an established twin cohort. We examined gender-specific associations between plasma adipokines and BP, with adjustment for measures of adiposity and insulin resistance (IR). We estimated the genetic contribution to adipokines using the twin design and Cholesky decomposition models. There was no correlation between leptin and adiponectin levels. Leptin was positively associated with systolic blood pressure (SBP) in males and diastolic blood pressure in females, but the association disappeared after adjusting for adiposity and IR. LAR was positively associated with SBP (β(s.e.): 1.94(0.45)), P<0.01), adiponectin was negatively associated with SBP (β(s.e.): -2.18(0.63)), P<0.001) only in males, and such associations were independent of adiposity and IR. A test of gender × adiponectin interaction was significant (P=0.01). Heritability estimation showed that both environmental and genetic factors contribute to variance in adipokines. In these relatively lean Chinese adolescents, leptin was positively associated with BP in both genders, but was adiposity/IR dependent. Adiponectin was negatively associated with SBP in males, independent of adiposity/IR.

Topics: Adipokines; Adiponectin; Adiposity; Adolescent; Age Factors; Asian People; Biomarkers; Blood Pressure; Chi-Square Distribution; China; Female; Genetic Predisposition to Disease; Humans; Hypertension; Insulin Resistance; Leptin; Logistic Models; Male; Multivariate Analysis; Odds Ratio; Prospective Studies; Risk Assessment; Risk Factors; Rural Health; Sex Factors; Twins; Young Adult

Circulating leptin is associated with cardiovascular events but the relationship between leptin and the clinical outcomes of intracerebral hemorrhage (ICH) is unclear. This study was to investigate the relationship between circulating leptin and the short-term clinical outcomes of ICH. Fifty-seven patients with hypertensive ICH (stroke group), 50 patients with hypertension (hypertension group), and 41 healthy subjects (control group) were recruited to this study. Serum levels of leptin were measured by radioimmunoassay. The serum level of leptin in the stroke group (14.6 ± 3.3 ng/L) was significantly higher than in the hypertension (10.2 ± 2.9 ng/L, P < 0.05) and control group (4.7 ± 3.3 ng/L, P < 0.01). Nine patients (15.8%) in the stroke group died during hospitalization. The mean National Institute of Health Stroke Scale (NIHSS) score of the surviving patients at admission and before discharge was 16 ± 6 and 9 ± 5, respectively (P < 0.01). There was a significant correlation between the serum leptin level and predischarge NIHSS scores (r = 0.62, P < 0.01). After adjusting age, sex, ICH volume and location, fasting blood glucose, fasting insulin levels, and systolic blood pressure (SBP) multivariate analysis showed that a high leptin level (>10 ng/L) was an independent predictor for in hospital mortality (adjusted risk ratio (RR), 3.6; 95% confidence interval (CI): 1.22-17.62; P = 0.02). In conclusion, serum leptin levels were increased in patients with hypertensive ICH. High leptin levels were associated with a poor functional recovery following ICH.

Topics: Aged; Aged, 80 and over; Blood Glucose; Case-Control Studies; Female; Humans; Hypertension; Insulin; Intracranial Hemorrhage, Hypertensive; Leptin; Male; Middle Aged; Multivariate Analysis; Prognosis; Prospective Studies

High leptin (LPT) is associated with high blood pressure (BP), insulin resistance and systemic inflammation but also excess body weight and adiposity. To disentangle these multiple relations, we analyzed BP, HOMA and circulating C-reactive protein concentration (hs-CRP) in white male adults with different LPT levels but similar age, body mass index (BMI) and body fat distribution. The novel aspect is the different statistical approach used to investigate the relation between LPT and the other alterations present in obesity.. 972 Olivetti Heart Study participants were stratified according to the median LPT distribution (2.97 ng/ml) into low LPT (l-LPT) and high LPT (h-LPT). The two groups were then carefully matched for age and BMI. We identified two groups of 207 h-LPT and 207 l-LPT individuals with overlapping age, BMI and waist/hip ratio. The two groups had different BP (132.9 ± 16.2/85.7 ± 9.0 vs 128.7 ± 18.2/82.8 ± 9.8 mmHg, p = 0.014 for SBP and p = 0.002 for DBP) and prevalence of hypertension (57% vs 43%, p = 0.027). Upon separate evaluation of untreated individuals with BMI < 25 or BMI ≥ 25, within the latter subgroup h-LPT compared with l-LPT participants (n = 133 each group) had higher BP (p = 0.0001), HOMA index (p = 0.013), hs-CRP (p = 0.002) and heart rate (p = 0.008) despite similar age and BMI. By contrast, within the normal weight subgroup, h-LPT individuals did not differ from l-LPT (n = 37 each) for any of these variables.. High LPT is associated with higher BP, HR, hs-CRP and HOMA index independently of BMI and fat distribution but only among overweight individuals.

Topics: Adiposity; Adult; Aged; Analysis of Variance; Biomarkers; Blood Pressure; Body Mass Index; C-Reactive Protein; Case-Control Studies; Humans; Hypertension; Inflammation; Inflammation Mediators; Insulin Resistance; Italy; Leptin; Linear Models; Logistic Models; Male; Middle Aged; Odds Ratio; Overweight; Risk Assessment; Risk Factors; Sex Factors; Up-Regulation

Leptin is a protein hormone, mainly synthesized in adipocytes, that regulates the food intake and energy expenditure of the body. Rare mutations in the leptin gene cause obesity. Common polymorphisms of the leptin gene have been associated with obesity, however their association with arterial blood pressure has not been fully elucidated. The aim of the present study was to examine the effect of variants in the 3' flanking region of the leptin gene on blood pressure in hypertensive subjects with high (35.2 ± 5.12) and low (20.13 ± 1.3) body mass index (BMI). Microsatellite polymorphisms and the C538T SNP in the 3'UTR of the leptin gene were screened in 362 subjects, and different biochemical and anthropometric parameters were measured. The levels of serum urea, creatinine, glucose, cholesterol, triglyceride, leptin and angiotensin II were determined in all subjects. A strong association of microsatellite polymorphisms with essential hypertension was found in subjects with a high BMI, but this association was only slight in subjects with a normal BMI. The C538T variant was not found in this population. The frequency of the Class I/Class I and Class I/Class II genotype for tetranucleotide polymorphisms was also significantly higher in the hypertensive compared to the normotensive group (p ≤ 0.0001). In addition, a significant correlation was found between serum leptin and Class I/I and Class I/II genotypes. Linear regression analysis showed an independent correlation of leptinemia with BMI (p=0.019), while a notable correlation was found between serum leptin concentration and angiotensin II. The study confirmed that shorter alleles of microsatellites in the 3' flanking region of leptin are significantly associated with hypertension, however, the underlying mechanism remains unknown.

Topics: 3' Untranslated Regions; Adult; Alleles; Angiotensin II; Blood Pressure; Body Mass Index; Female; Genotype; Humans; Hypertension; Leptin; Male; Microsatellite Repeats; Middle Aged; Polymorphism, Genetic; Polymorphism, Single Nucleotide

There is evidence that obesity is associated with increased sympathetic activity and hypertension. However, the mechanisms responsible for these changes are not fully understood. Therefore, the aim of the present study was to evaluate the cardiovascular function and the baroreceptor reflex control of renal sympathetic nerve activity (rSNA) in rats exposed to a high-fat diet over different periods (10 and 20 weeks) compared to control rats. Serum leptin levels were assessed for all time points. Male Wistar rats weighing 150-180 g were used. Four groups of rats were studied: control 10 weeks (Ct10), obese 10 weeks (Ob10), control 20 weeks (Ct20), and obese 20 weeks (Ob20). Blood pressure (BP) and rSNA were recorded in urethane-anesthetized rats (1.4 g/kg, intravenous).The sensitivity of rSNA responses to baroreceptor reflex was assessed by changes in BP induced by increasing doses of phenylephrine or sodium nitroprusside. Significant and progressive increases in serum leptin levels were found in the obese rats, but not in the control rats. No changes in basal BP or rSNA were found in the Ob10 and Ob20 groups; however, a significant impairment in the baroreceptor sensitivity was observed in the Ob20 group for phenylephrine (slope Ob20: -0.78 ± 0.12 vs. Ct20: -1.00 ± 0.08 potential per second (pps)/mm Hg, P < 0.05) and sodium nitroprusside (slope Ob20: -0.82 ± 0.09 vs. 1.13 ± 0.13 pps/mm Hg, P < 0.05). The results suggest that the baroreceptor dysfunction that controls the rSNA is an initial change in the obesity induced in high-fat-fed rats, which might be a predictor of sympathoexcitation and hypertension associated to obesity.

Topics: Animals; Baroreflex; Blood Pressure; Diet, High-Fat; Hypertension; Kidney; Leptin; Male; Nitroprusside; Obesity; Phenylephrine; Rats; Rats, Wistar; Sympathetic Nervous System; Vasoconstrictor Agents; Vasodilator Agents

The finding of adipocyte-derived hormone leptin as an overstimulator of sympathetic activity brought a new perspective to the pathophysiological mechanisms of obesity-hypertension.. As aldosterone also increases sympathetic activity, we aimed to assess the relationship between sympathetic overactivity and plasma leptin and aldosterone levels in resistant hypertension (RHTN), comparing the groups with and without T2D.. Twenty-five RHTN patients underwent ambulatory electrocardiography to analyze heart rate variability (HRV) in time and frequency domains, which were stratified into two periods: 24 hours and daytime (DT), comprising the records between 2:00 p.m to 6:00 p.m (time domain) and one hour at 3:00 p.m (frequency domain).. T2D group (n=10) had higher serum aldosterone and plasma leptin levels than the non-T2D (n=15) (26.0 ± 11.5 vs. 16.9 ± 7.0 ng/dL - p=0.021; 81.368.7 ± 47.086.1 vs 41.228.1 ± 24.523.1 pg/mL - p=0.048, respectively). Both groups had aldosterone correlated with HRV in frequency domain. Non-T2D had aldosterone correlated with DT low frequency in normalized units (LF nu) (r=0.6 [0.12-0.85] p=0.018) and DT high frequency in normalized units (HF nu) (r=-0.6 [-0.85- -0.12] p=0.018). Type-2-diabetes group had aldosterone correlated with DT LF nu (r=0.72 [0.16-0.93] p=0.019) and DT HF nu (r=-0.72 [-0.93- -0.16] p=0.019). However, despite of the importance of leptin in sympathetic overactivity in hypertension, leptin did not correlate with HRV.. Aldosterone seems to overdrive sympathetic activity in RHTN with and without T2D. This information combined with the clinical efficacy of mineralocorticoid receptor blocker in RHTN may reinforce that aldosterone is a major player to be a therapeutic target in RHTN.

Topics: Adult; Aldosterone; Antihypertensive Agents; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Diabetes Mellitus, Type 2; Drug Resistance; Female; Heart Rate; Humans; Hypertension; Leptin; Male; Middle Aged; Statistics, Nonparametric; Sympathetic Nervous System

Hypertension and elevated sympathetic drive result from consumption of a high-calorie diet and deposition of abdominal fat, but the etiology and temporal characteristics are unknown. Rabbits instrumented for telemetric recording of arterial pressure and renal sympathetic nerve activity (RSNA) were fed a high-fat diet for 3 weeks then control diet for 1 week or control diet for 4 weeks. Baroreflexes and responses to air-jet stress and hypoxia were determined weekly. After 1 week of high-fat diet, caloric intake increased by 62%, accompanied by elevated body weight, blood glucose, plasma insulin, and leptin (8%, 14%, 134%, and 252%, respectively). Mean arterial pressure, heart rate, and RSNA also increased after 1 week (6%, 11%, and 57%, respectively). Whereas mean arterial pressure and body weight continued to rise over 3 weeks of high-fat diet, heart rate and RSNA did not change further. The RSNA baroreflex was attenuated from the first week of the diet. Excitatory responses to air-jet stress diminished over 3 weeks of high-fat diet, but responses to hypoxia were invariant. Resumption of a normal diet returned glucose, insulin, leptin, and heart rate to control levels, but body weight, mean arterial pressure, and RSNA remained elevated. In conclusion, elevated sympathetic drive and impaired baroreflex function, which occur within 1 week of consumption of a high-fat, high-calorie diet, appear integral to the rapid development of obesity-related hypertension. Increased plasma leptin and insulin may contribute to the initiation of hypertension but are not required for maintenance of mean arterial pressure, which likely lies in alterations in the response of neurons in the hypothalamus.

Topics: Adiposity; Analysis of Variance; Animals; Baroreflex; Blood Glucose; Blood Pressure; Body Weight; Diet, High-Fat; Dietary Fats; Heart Rate; Hypertension; Insulin; Kidney; Leptin; Male; Obesity; Rabbits; Sympathetic Nervous System; Time Factors

The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.

Topics: Adiponectin; Animals; Constitutive Androstane Receptor; Diet, High-Fat; Female; Glucose Tolerance Test; Hyperglycemia; Hypertension; Insulin Resistance; Leptin; Mice; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Pyridines; Receptors, Cytoplasmic and Nuclear; Triglycerides

Acute studies suggest that adiponectin may reduce sympathetic activity and blood pressure (BP) via actions on the central nervous system (CNS). However, the chronic effects of adiponectin on energy expenditure and cardiovascular function are still poorly understood. We tested if chronic intracerebroventricular (ICV) infusion of adiponectin (1 or 7μg/day) in Sprague-Dawley rats fed a high fat diet (HFD) for 8 weeks and at the high dose (7μg/day) in spontaneously hypertensive rats (SHRs), a hypertensive model associated with sympathetic overactivity, evoked chronic reductions in BP and heart rate (HR). We also determined if chronic ICV adiponectin infusion alters appetite, whole body oxygen consumption (VO(2)), and insulin and leptin levels. Neither dose of adiponectin infused for 7 days significantly altered BP or HR in the HFD group (115±2 to 112±2mmHg and 384±6 to 379±6bpm at 1μg/day; 109±3 to 111±3mmHg and 366±5 and 367±5bpm at 7μg/day). The higher dose slightly reduced food intake (14±1 to 11±1g/day), whereas VO(2), insulin and leptin levels were not affected by the treatment. In SHRs, ICV adiponectin infusion reduced appetite (22±2 to 12±2g/day) and insulin levels (∼55%), but did not alter BP (162±4 to 164±3mmHg) or HR (312±5 to 322±8bpm). These results suggest that adiponectin, acting via its direct actions on the CNS, has a small effect to reduce appetite and insulin levels, but it has no long-term action to reduce BP or HR, or to alter whole body metabolic rate.

Topics: Adiponectin; Animals; Antihypertensive Agents; Appetite; Blood Glucose; Blood Pressure; Diet, High-Fat; Fructose; Heart Rate; Hypertension; Infusions, Intraventricular; Insulin; Leptin; Male; Motor Activity; Oxygen Consumption; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley

The alarming increase in obesity worldwide is of concern, owing to the associations of obesity with metabolic syndrome (MetS), which has been associated with a proinflammatory state characterized by elevated plasma concentrations of several markers of inflammation. The aim of this study was to assess levels of inflammatory markers and their association with MetS among adolescents.. A random sample of adolescents (n=362, 143 boys and 219 girls, 12-17 years) was interviewed, anthropometrically measured and provided a fasting blood sample. Circulating levels of adiponectin, leptin, tumour necrosis factor-alpha, plasminogen activator inhibitor 1 (PAI-1), interleukin-6 and high-sensitivity C-reactive protein were measured. The association between inflammatory markers and sex, age, body mass index (BMI) status, MetS, physical activity and blood pressure was also calculated.. Adiponectin levels are inversely associated and leptin levels are directly associated with MetS and BMI, but directly with gender (females show higher levels than boys), and PAI-1 levels are directly associated with MetS, among adolescents.. Leptin, adiponectin and PAI-1 may be used as biomarkers to predict MetS among adolescents.

Topics: Adiponectin; Adolescent; Biomarkers; Body Mass Index; C-Reactive Protein; Child; Cross-Sectional Studies; Down-Regulation; Female; Humans; Hypertension; Inflammation Mediators; Leptin; Male; Mediterranean Islands; Metabolic Syndrome; Overweight; Plasminogen Activator Inhibitor 1; Predictive Value of Tests; Prevalence; Spain; Up-Regulation

Adipose tissue possess endocrine functions that include synthesis of various adipocytokines, which affect the metabolism of lipids and glucoses, development of atherosclerotic processes, and are involved in the development of hypertension and cardiovascular diseases. Body fat distribution is a significant risk factor for the development of obesity related diseases. Leptin and adiponectin are adipokines whose concentrations vary with the level of obesity. The aim of this research is to determine the relation of the changes in leptin and adiponectin concentrations in overweight persons with anthropometric parameters of the subjects.. The study included 40 adult, hypertensive subjects - divided into two groups according to sex, with the body mass index 25-30 kg/m², with regular glycemia and renal function. All subjects underwent biochemical (serum lipid, glucose and creatinine level) and anthropometric measurements. Leptin concentration was determined by radioimmunoassay, while adiponectin concentration was determined by enzyme immunoassay.. Both leptin and adiponectin concentrations significantly correlated with the waist circumference in both groups of subjects. In male subjects, leptin concentration correlated positively with the body mass index and the hip circumference, while adiponectin concentration correlated negatively with the hip circumference.. Being overweight is a condition marked by pathologically altered values of leptin concentration (increased level) and adiponectin (decreased level), that are changing as the obesity level and the waist circumference increase. It can be concluded that abdominal obesity and higher body mass index increase the risk for the development of overweight-obesity-related diseases.

Topics: Adiponectin; Adult; Body Mass Index; Body Size; Cardiovascular Diseases; Female; Humans; Hypertension; Leptin; Male; Overweight; Waist Circumference

to investigate whether body mass index (BMI), hypertension (HTN), diabetes, age, and physical activity can be considered risk factors for endometrial simple hyperplasia in premenopausal women. Furthermore this study was undertaken to determine whether serum concentration of leptin in patients with BMI>or= 30 kg / m2 with endometrial hyperplasia deviate from values in patients with normal endometrium.. The authors enrolled 167 hyperplasia cases and 282 controls. Demographic characteristics and data on age, diabetes, hypertension, BMI, physical activity, and anthropometric parameters were collected. Leptin concentration in serum was measured with immunoenzymatic test kit from IBL. Univariable and multivariable analysis were performed to verify the association among age, HTN, BMI, physical activity, diabetes, and the presence of uterine hyperplasia. Furthermore the authors evaluated the correlation between BMI and leptin level (with Pearson's linear correlation) in women with simple hyperplasia and in controls.. The prevalence of hyperplasia found was 34.4%. The following factors were independently associated with increased risk of endometrial hyperplasia: HTN (odds ratio 3.19, 95% confidence interval 1.20-8.48, p<0.020) and BMI>or=30 Kg/m2 (odds ratio 6.43, 95% confidence interval 3.92-10.53, p<0.000). Mean leptin concentration in serum was higher in patients who had endometrial hyperplasia than in controls (p<0.005) and the leptin levels depended on BMI.. The following are risk factors for endometrial hyperplasia in premenopausal women: BMI>or=30 kg/m2 and HTN (blood pressure>or=130/85 or in therapy). Leptin appears to participate in proliferative processes of the endometrium, depending on BMI. Current guidelines may need to be reconsidered.

Topics: Adult; Age Factors; Body Mass Index; Endometrial Hyperplasia; Exercise; Female; Humans; Hypertension; Leptin; Middle Aged; Obesity; Premenopause; Risk Factors; Waist-Hip Ratio

Obstructive sleep apnoea syndrome (OSAS) causes nocturnal chronic intermittent hypoxia (IH) that contributes to excess cardiovascular morbidity. To explore the consequences of IH, we used our recently developed model of nocturnal IH in healthy humans to characterise the profile of this blood pressure increase, to determine if it is sustained and to explore potential physiological mechanisms. We performed 24-h ambulatory monitoring of blood pressure in 12 healthy subjects before and after 2 weeks of IH exposure. We also assessed systemic haemodynamics, muscle sympathetic nerve activity (MSNA), ischaemic calf blood flow responses and baroreflex gain. We obtained blood samples for inflammatory markers before, during and after exposure. IH significantly increased daytime ambulatory blood pressure after a single night of exposure (3 mmHg for mean and diastolic) and further increased daytime pressures after 2 weeks of exposure (8 mmHg systolic and 5 mmHg diastolic). Mean ± sd MSNA increased across the exposure (17.2 ± 5.1 versus 21.7 ± 7.3 bursts·min⁻¹; p < 0.01) and baroreflex control of sympathetic outflow declined from -965.3 ± 375.1 to -598.4 ± 162.6 AIU·min⁻¹ ·mmHg⁻¹ (p < 0.01). There were no evident changes in either vascular reactivity or systemic inflammatory markers. These data are the first to show that the arterial pressure rise is sustained throughout the waking hours beyond the acute phase immediately after exposure. Moreover, they may suggest that sympathoactivation induced by IH likely contributes to blood pressure elevation and may derive from reduced baroreflex inhibition. These mechanisms may reflect those underlying the blood pressure elevation associated with OSAS.

Topics: Adiponectin; Adult; Blood Pressure; Body Mass Index; C-Reactive Protein; Chemokine CCL5; Female; Humans; Hypertension; Hypoxia; Intercellular Adhesion Molecule-1; Interleukin-8; Leptin; Male; Receptors, Interleukin-1; Sleep Apnea Syndromes; Sympathetic Nervous System; Tumor Necrosis Factor-alpha

Stress in combination with genetic susceptibility is a factor in the development of hypertension. We used borderline hypertensive rats to investigate whether exposure to high-fat and/or junk-food diet at different stages of ontogeny has programing consequences on stress responses. Wistar dams were fed a high- or low-fat diet for 6 weeks prior to mating with spontaneously hypertensive males, and during gestation. At birth, litters were fostered either to a dam in the same or an alternative diet condition as during gestation. After weaning, male offspring were fed either a control-chow diet or an intermittent junk food fatty diet. Between postnatal days 57-61, half of the rats in each dietary group received daily social defeat sessions using a resident-intruder protocol, and the other half were unstressed controls. Blood pressure was measured indirectly both before and after each defeat session. On the final day, rats were killed for physiological measures. Socially defeated rats showed large increases in serum corticosterone concentration and adrenal hypertrophy, indicating the effectiveness of this non-adapting stressor. Serum corticosterone level was also higher in rats fed with the junk-food diet post-weaning compared with those fed with chow only, but there were no significant effects of gestational or lactational dietary history.

Topics: Adipose Tissue; Animals; Blood Pressure; Dietary Fats; Dominance-Subordination; Female; Hypertension; Leptin; Male; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred SHR; Rats, Wistar; Stress, Psychological

The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome.

Topics: Abdominal Fat; Animals; Body Weight; Diabetes Mellitus, Experimental; Dietary Carbohydrates; Dietary Fats; Energy Intake; Fructose; Glucose Intolerance; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Liver; Male; Metabolic Syndrome; Obesity; Random Allocation; Rats; Rats, Wistar; Ventricular Remodeling

Premature delivery is often complicated by neonatal growth restriction (GR) and neurodevelopmental impairment. Because global overnutrition increases the risk of adult metabolic syndrome, we sought a targeted intervention. Premature delivery and perinatal GR decrease circulating levels of the neurotrophic hormone leptin. We hypothesized that leptin supplementation would normalize the outcomes of mice with incipient neonatal GR. Pups were fostered into litters of 6 or 12 to elicit divergent growth patterns. Pups in each litter received injections of saline or leptin from d 4 to 14. At 4 mo, mice underwent tail cuff blood pressure measurement, behavioral testing, and MRI. Mice fostered in litters of 12 had decreased weanling weights and leptin levels. Neonatal leptin administration normalized plasma leptin levels without influencing neonatal growth. Leptin replacement also normalized the hypertension, stress-linked immobility, conditioned fear, and amygdala enlargement seen in neonatal growth restricted male mice. In control males, neonatal leptin administration led to hypothalamic enlargement, without overt neurocardiovascular alterations. Female mice were less susceptible to the effects of neonatal GR or leptin supplementation. In conclusion, the effects of neonatal leptin administration are modulated by concurrent growth and gender. In growth restricted male mice, physiologic leptin replacement improves adult neurocardiovascular outcomes.

Topics: Age Factors; Aging; Amygdala; Animals; Animals, Newborn; Behavior, Animal; Blood Pressure; Body Weight; Cardiovascular System; Conditioning, Psychological; Fear; Female; Hypertension; Injections, Intraperitoneal; Leptin; Litter Size; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Motor Activity; Organ Size; Phenotype; Sex Factors

We examined whether systemic or central nervous system (CNS) inhibition of nitric oxide synthase exacerbates the cardiovascular responses of chronic CNS melanocortin 3/4 receptor activation. Sprague-Dawley rats implanted with telemetry probes, venous catheters, and intracerebroventricular (ICV) cannulae were divided in 3 groups. After control measurements, the NO synthase inhibitor L-NAME was infused (10 μg/kg/min intravenous) for 17 days and, starting on day 7 of L-NAME infusion, the melanocortin 3/4 receptor agonist melanotan II (MTII; 10 ng/hr; group 1) or saline vehicle (group 2) was infused ICV for 10 days. A third group not treated with L-NAME also received MTII ICV. Melanocortin 3/4 receptor activation caused a greater increase in mean arterial pressure (MAP) and heart rate in rats treated with intravenous L-NAME (35 ± 6 mm Hg and 56 ± 8 bpm) than L-NAME plus vehicle or MTII alone (22 ± 5 and 9 ± 2 mm Hg, and 26 ± 14 and 27 ± 5 bpm), despite a 58% and 50% reduction in food intake during the first 6 days of MTII infusion. To test if the amplified pressor response to MTII after L-NAME was attributable to a reduction in nitric oxide availability in the brain, we also infused L-NAME directly into the CNS alone or in combination with MTII. ICV infusion of L-NAME plus MTII caused only ≈ 10 mm Hg increase in MAP with no change in heart rate, similar to the effects of ICV infusion of MTII alone, whereas ICV infusion of L-NAME alone had no effect on MAP. These results suggest that reduction in peripheral, but not CNS, nitric oxide production augments MAP sensitivity to CNS melanocortin 3/4 receptor activation.

Topics: alpha-MSH; Analysis of Variance; Animals; Blood Glucose; Body Weight; Catheters, Indwelling; Eating; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Hypertension; Insulin; Leptin; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Peptides, Cyclic; Rats; Rats, Sprague-Dawley; Receptor, Melanocortin, Type 3; Receptor, Melanocortin, Type 4; Telemetry

We assessed the contribution of angiotensin-(1-7) [Ang-(1-7)] to captopril-induced cardiovascular protection in spontaneously hypertensive rats (SHRs) chronically treated with the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (SHR-l). NG-nitro-L-arginine methyl ester (80 mg/L) administration for 3 weeks increased mean arterial pressure (MAP) from 196 ± 6 to 229 ± 3 mm Hg (P < 0.05). Treatment of SHR-l with Ang-(1-7) antagonist [d-Ala7]-Ang-(1-7) (A779; 744 μg·kg(-1)·d(-1) ip) further elevated MAP to 253 ± 6 mm Hg (P < 0.05 vs SHR-l or SHR). Moreover, A779 treatment attenuated the reduction in MAP and proteinuria by either captopril (300 mg/L in drinking water) or hydralazine (1.5 mg·kg(-1)·d(-1) ip). In isolated perfused hearts, the recovery of left ventricular function from global ischemia was enhanced by captopril or hydralazine treatment and was exacerbated with A779. The Ang-(1-7) antagonist attenuated the beneficial effects of captopril and hydralazine on cardiac function. Recovery from global ischemia was also improved in isolated SHR-l hearts acutely perfused with captopril during both the perfusion and reperfusion periods. The acute administration of A779 reduced the beneficial actions of captopril to improve recovery after ischemia. We conclude that during periods of reduced nitric oxide availability, endogenous Ang-(1-7) plays a protective role in effectively buffering the increase in blood pressure and renal injury and the recovery from cardiac ischemia. Moreover, Ang-(1-7) contributes to the blood pressure lowering and tissue protective actions of captopril and hydralazine in a model of severe hypertension and end-organ damage.

Topics: Angiotensin I; Angiotensin II; Animals; Antihypertensive Agents; Blood Glucose; Blood Pressure; Brain; Captopril; Cytokines; Heart; Hydralazine; Hypertension; In Vitro Techniques; Insulin; Kidney; Leptin; Male; Myocardial Contraction; Myocardial Reperfusion Injury; NG-Nitroarginine Methyl Ester; Peptide Fragments; Perfusion; Proteinuria; Rats; Rats, Inbred SHR; Ventricular Function, Left

Multidetector row computed tomography (MDCT) enables the accurate noninvasive assessment of coronary artery stenosis and plaque imaging. The characteristics of patients who have coronary artery disease (CAD) as assessed by MDCT coronary computed tomography (CT) are not well known. Participants consisted of 513 consecutive patients with suspected CAD who underwent coronary CT. The authors quantified patient characteristics, including the prevalence of hypertension (HTN), hyperlipidemia and diabetes mellitus (DM), visceral fat area (VFA) and subcutaneous fat area using CT, and plasma levels of metabolic factors, including adiponectin and leptin. Although plasma levels of adiponectin in men and leptin in women were significantly associated with chronic kidney disease, there were no differences in these levels between patients with and without CAD. HTN was most significantly associated with the presence of CAD by multivariate logistic regression analysis (men, P=.002; women, P=.048). Finally, the percentage of CAD significantly increased as systolic blood pressure increased (trend, P=.0002) in men but not women. In conclusion, hypertension was significantly associated with CAD as assessed by coronary CT.

Topics: Adiponectin; Aged; Body Mass Index; Coronary Artery Disease; Cross-Sectional Studies; Female; Health Status Indicators; Humans; Hypertension; Japan; Leptin; Logistic Models; Male; Middle Aged; Prevalence; Risk Assessment; Risk Factors; Systole; Tomography, X-Ray Computed

Extreme replacement of skeletal muscles by adipose tissue was found in an 86-year old Japanese male cadaver during dissection practice for medical students at Oita University School of Medicine. Especially, the bilateral sartorius muscles looked overall like adipose tissue. The man had suffered from diabetes mellitus, renal failure, hypertension and hypothyroidism before his death. He was also an alcohol drinker. He had been bedridden late in life. The cause of death was renal failure. In microscopy, the adipose tissue-like sartorius muscle was shown to consist of leptin-positive adipocytes with a small number of degenerated muscle fibers. Fatty replacement, or fatty degeneration, appears to result from endocrine and metabolic disorders, and being bedridden leads to muscle atrophy and damage, although the origin of the adipocytes which emerged in the degenerated muscles is unknown.

Topics: Adipocytes, White; Adipose Tissue, White; Aged, 80 and over; Body Fat Distribution; Cadaver; Comorbidity; Diabetes Mellitus; Humans; Hypertension; Hypothyroidism; Leptin; Male; Muscle, Skeletal; Renal Insufficiency

Mechanisms underlying obesity-related vascular dysfunction are unclear. This study examined the effect of diet-induced obesity on expression and function of large conductance Ca(2+)-activated potassium channel (BK(Ca)) in rat pressurized small resistance vessels with myogenic tone. Male Sprague-Dawley rats fed a cafeteria-style high fat diet (HFD; ∼30% energy from fat) for 16-20 wk were ∼30% heavier than controls fed standard chow (∼13% fat). Obesity did not alter BK(Ca) α-subunit function or α-subunit protein or mRNA expression in vessels isolated from the cremaster muscle or middle-cerebral circulations. In contrast, BK(Ca) β(1)-subunit protein expression and function were significantly reduced in cremaster muscle arterioles but increased in middle-cerebral arteries from obese animals. Immunohistochemistry showed α- and β(1)-subunits were present exclusively in the smooth muscle of both vessels. Cremaster muscle arterioles from obese animals showed significantly increased medial thickness, and media-to-lumen ratio and pressurized arterioles showed increased myogenic tone at 30 mmHg, but not at 50-120 mmHg. Myogenic tone was not affected by obesity in middle-cerebral arteries. The BK(Ca) antagonist iberiotoxin constricted both cremaster muscle and middle-cerebral arterioles from control rats; this effect of iberiotoxin was abolished in cremaster muscle arteries only from obese rats. Diet-induced obesity has contrasting effects on BK(Ca) function in different vascular beds, through differential effects on β(1)-subunit expression. However, these alterations in BK(Ca) function had little effect on overall myogenic tone, suggesting that the mechanisms controlling myogenic tone can be altered and compensate for altered BK(Ca) expression and function.

Topics: Animals; Arterioles; Blotting, Western; Cerebral Arteries; Diet; Dietary Fats; Energy Intake; Heart Rate; Hyperinsulinism; Hypertension; Immunohistochemistry; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; Leptin; Male; Microscopy, Electron; Muscle Tonus; Muscle, Skeletal; Obesity; Potassium Channels; Rats; Rats, Sprague-Dawley; Regional Blood Flow; Reverse Transcriptase Polymerase Chain Reaction; Weight Gain

Although the anorexic effects of leptin are lost in obesity, leptin-mediated sympatho-activation is preserved. The cardiovascular consequences of leptin-mediated sympatho-activation in obesity are poorly understood. We tested the hypothesis that 32 weeks of high-fat diet (HFD) induces metabolic leptin resistance but preserves leptin-mediated sympatho-activation of the cardiovascular system. HFD in mice significantly increased body weight and plasma leptin concentrations but significantly reduced the anorexic effects of leptin. HFD increased heart rate, stroke volume, cardiac output, and plasma aldosterone levels but not blood pressure. As reflected by the contractile response to phenylephrine measured both in vivo and ex vivo, vascular adrenergic reactivity was reduced by HFD, suggesting that reductions in sympathetic tone to the periphery vasculature may mitigate sympatho-activation of the heart and the renin-angiotensin-aldosterone system. Tachyphylaxis was partially restored by symptho-inhibition and not present in ob/ob and db/db mice, despite obesity, arguing for a sympatho-mediated and leptin-specific mechanism. Although infusion of leptin in HFD mice had no effect on heart rate or blood pressure, it further increased aldosterone levels and further reduced vascular adrenergic tone in the absence of weight loss, indicating persistent leptin-mediated stimulation of the cardiovascular system in obesity. In conclusion, these data indicate that, despite metabolic leptin resistance, leptin-mediated stimulation of the heart, the vasculature, and aldosterone production persists in obesity. Blood pressure effects in response to leptin may be limited by a tachyphylactic response in the circulation, suggesting that failure of adrenergic desensitization may be a requisite step for hypertension in the context of obesity.

Topics: Aldosterone; Animals; Blood Pressure; Cardiovascular System; Dietary Fats; Heart Rate; Hypertension; Leptin; Male; Mice; Obesity; Renin-Angiotensin System; Sympathetic Nervous System

Despite the higher prevalence of diabetes and hypertension in populations residing at moderate altitudes, mortality in these populations is lower than in populations residing at low altitudes. To examine whether metabolic and hemodynamic differences can explain this apparent paradox, we performed a cross-sectional study of a general population sample recruited in the Canary Islands, Spain (n=6729). We recorded altitude of residence, age, heart rate, blood pressure, body mass index, social class, physical activity, energy intake, alcohol intake, smoking habit, prevalence of type 2 diabetes mellitus and hypertension. In a subsample (n=903), we recorded serum concentration of cholesterol, triglycerides, glucose, C peptide, leptin, soluble leptin receptor (sObR), C-reactive protein, resistin, soluble CD40 ligand (sCD40L), and paraoxonase activity (PON), and we estimated insulin resistance and free leptin index. We found an inverse association between altitude and heart rate (p<0.001), leptin (p<0.001), free leptin index (p<0.001), resistin (p<0.001), and sCD40L (p<0.05) and a direct association between altitude and hypertension (odds ratio=1.29 for altitude >600 m; 95% confidence interval=1.03-1.62), glycemia (p<0.05), C peptide (p<0.001), insulin resistance (p<0.001), sObR (p<0.05), and PON (p<0.05). When social class was included in the multivariate model, the association with PON was no longer significant. In conclusion, individuals residing at moderate altitudes have a lower heart rate and lower serum concentration of total leptin, free leptin, and sCD40L. These differences may partially explain the lower mortality in these populations.

Topics: Adolescent; Adult; Aged; Altitude; Blood Pressure; CD40 Ligand; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Energy Metabolism; Female; Heart Rate; Hemodynamics; Humans; Hypertension; Inflammation; Insulin Resistance; Leptin; Lipid Metabolism; Male; Middle Aged; Young Adult

Interleukin 1 beta (IL-1β) is a proinflammatory cytokine with potent cardiosuppressive effects. Previous studies have shown that leptin blunts the negative inotropic effects of IL-1β in isolated adult rat cardiac myocytes. However, the interactions between leptin and IL-1β in the heart have not been examined on a background of chronic hyperleptinemia. To study this interaction, we have chosen the SHHF rat, a model of spontaneous hypertension that ultimately develops congestive heart failure. SHHF that are heterozygous for a null mutation of the leptin receptor (+/fa(cp), HET) are phenotypically lean but chronically hyperleptinemic and develop heart failure earlier than their normoleptinemic true lean (+/+, LN) littermates. Simultaneous cell shortening and calcium transients were measured in isolated ventricular cardiac myocytes from LN and HET SHHF in response to leptin, IL-1β or IL-1β following one hour pretreatment with leptin. Despite evidence of metabolic leptin resistance, HET myocytes were sensitive to the negative inotropic effect of leptin, similar to LN. Contractility returned to control levels in myocytes from HET that were pretreated with leptin prior to IL-1β, while contractility remained depressed compared with control and similar to leptin alone in LN. Chronic hyperleptinemia resulted in altered JAK/STAT signaling in response to leptin and IL-1β in isolated perfused hearts from HET compared with LN SHHF. Phosphorylated STAT3 (pSTAT3) and STAT5 (pSTAT5) decreased when HET hearts were treated with leptin followed by IL-1β. While decreases in pSTAT3 and pSTAT5 may be associated with abrogation of the acute negative inotropic effects of IL-1β in the presence of leptin in HET, long-term consequences remain to be explored. This study demonstrates that the heart remains sensitive to leptin in a hyperleptinemic state. Crosstalk between leptin and IL-1β can influence cardiac function and cytokine signaling and these interactions are moderated by the presence of long-term hyperleptinemia.

Topics: Animals; Disease Models, Animal; Hypertension; Interleukin-1beta; Leptin; Male; Myocytes, Cardiac; Rats; Rats, Inbred Strains; Receptors, Leptin; Signal Transduction

In children, blood pressure (BP) and risk for hypertension are proportional to degree of adiposity. Whether the relationship to BP is similar over the full range of adiposity is less clear. Subjects from a cohort study (n=1111; 50% male and 42% black) contributed 9102 semiannual BP and height/weight assessments. The mean enrollment age was 10.2 years, and mean follow-up was 4.5 years. Adiposity was expressed as body mass index percentile, which accounted for effects of age and sex. The following observations were made. The effect of relative adiposity on BP was minimal until the body mass index percentile reached 85, beginning of the overweight category, at which point the effect of adiposity on BP increased by 4-fold. Similarly intensified adiposity effects on BP were observed in children aged ≤10, 11 to 14 years, and ≥15 years. Serum levels of the adipose tissue-derived hormone, leptin, together with heart rate, showed an almost identically patterned relation to BP to that of body mass index percentile and BP, thus implicating a possible mediating role for leptin. In conclusion, there is a marked intensification of the influence of adiposity on BP when children reach the categories of overweight and obese. Among the possible pathways, leptin may be a potentially important mediator acting through the sympathetic nervous system (reflected in heart rate). The findings have relevance to interventions designed to prevent or treat adiposity-related increases in BP and to the analytic approaches used in epidemiological studies.

Topics: Adiposity; Adolescent; Age Factors; Anthropometry; Blood Pressure Determination; Body Mass Index; Child, Preschool; Cross-Sectional Studies; Female; Humans; Hypertension; Leptin; Male; Obesity; Overweight; Prevalence; Radioimmunoassay; Risk Assessment; United States

OBJECTIVE. The mechanisms by which overweight and physical inactivity lead to hypertension are complex. Leptin, an adipocyte-derived hormone, has been linked with hypertension. We wanted to investigate the relationship between leptin, physical activity and new-onset hypertension. METHODS. The study was a prospective cohort study of 744 women and 367 men, who were normotensive in the third Copenhagen City Heart Study (CCHS) examination, performed 1991−94. Based on questionnaire items, the participants were divided into two groups with low (n = 674) and high (n = 437) levels of leisure-time physical activity, respectively. RESULTS. Between the third and the fourth CCHS examination, performed 2001?03, 304 had developed hypertension, defined as systolic blood pressure (SBP) ≥140 mmHg or diastolic blood pressure (DBP) ≥90 mmHg or use of antihypertensive medication. In a logistic regression model, including age, sex, body mass index, SBP, DBP, level of physical activity and leptin, we found a significant interaction between leptin and level of physical activity with new-onset hypertension as outcome variable (p = 0.012). When we entered the interaction variables, effect of leptin with low level of physical activity and with high level of physical activity, respectively, in the original model, leptin predicted new-onset hypertension in participants with low level of physical activity [odds ratio (95% confidence interval): 1.16 (1.01−1.33) for one unit increase in log-transformed leptin levels, p = 0.038], but not in participants with high level of physical activity [0.88 (0.74−1.05), p = 0.15]. CONCLUSION. We found that leptin predicted new-onset hypertension but only in participants with low level of physical activity.

Topics: Adiponectin; Adult; Antihypertensive Agents; Blood Pressure; Body Mass Index; Denmark; Diastole; Female; Follow-Up Studies; Humans; Hypertension; Immunoassay; Leptin; Logistic Models; Male; Middle Aged; Motor Activity; Odds Ratio; Prospective Studies; Risk Factors; Surveys and Questionnaires; Systole

Along with the growing epidemic of overweight the risk of atherosclerosis, cardiovascular disease morbidity and mortality are increasing markedly. Metabolic syndrome (MS) is a condition clustering together several risk factors of those complications such as visceral obesity, glucose intolerance, arterial hypertension and dislipidemia. The risk of obesity in acute lymphoblastic leukemia (ALL) survivors is higher than in general population. We aimed to assess (1) the relationships between chosen adipokines and neuropeptides, chemotherapy, CRT, and body fatness and (2) evaluate adipokines and neuropeptides concentrations as a new markers of MS in children. We conducted cross-sectional evaluation of 82 ALL survivors (median age: 13.2 years; range: 4,8-26,2; median time from treatment: 3.2 years), including fasting laboratory testing: peptides (leptin, GLP-1, orexin, PYY, apelin), total cholesterol and its fractions, triglycerides; anthropometric measurements (weight, height), systolic and diastolic blood pressure. We estimated percentiles of body mass index and percentiles of blood pressure. Between 82 survivors overweight and diastolic hypertension was diagnosed in 31% of patients (35% in CRT group) and 15% respectively. At least one abnormality in lipids concentrations was found in 43%. Girls were more affected than boys. Statistically significant increased in leptin and apelin concentrations and decreased in soluble leptin receptor concentrations in the overweight group were observed compared to the non overweight subjects. Significant increase in orexin levels in females who had received CRT compared to those who had not received CRT was found. CRT is the main risk factor of elevated of body mass among survivors of childhood leukemia. Dyslipidemia and hypertension, along with increased adiposity indicate higher risk of MS development. Girls are more affected than boys. Leptin, orexin and apelin seem to be good markers of increased adiposity especially after CRT. Higher leptin levels may be related to central resistance to those peptides. Survivors of childhood acute lymphoblastic leukemia should be screened for markers of the metabolic syndrome.

Topics: Adipokines; Adolescent; Adult; Age Distribution; Biomarkers; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Hypertension; Intracellular Signaling Peptides and Proteins; Leptin; Male; Metabolic Syndrome; Neuropeptides; Obesity; Orexins; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors; Young Adult

Leptin is mainly secreted from adipose tissue and is known to be associated with cardiovascular diseases. However, there are not many studies on the association between serum leptin and metabolic syndrome. The objective of this study was to determine the association between serum leptin and metabolic syndrome among the Korean adult population. The study population consisted of 3,272 Koreans (men: 1,915, women: 1,357) 30 to 84 years of age who had visited the Health Examination Center. Leptin levels were divided into quintiles and metabolic syndrome was defined by NCEP ATP III. The serum leptin levels increased as the number of components present for metabolic syndrome increased. Controlling for age, smoking, exercise, and LDL cholesterol, subjects with high leptin levels were more likely to have an elevated risk of metabolic syndrome than those with lower levels in both men and women. Subjects in the highest leptin quintile were found to have a higher risk of having metabolic syndrome than those in the lowest quintile (OR = 11.51 for men; OR = 4.65 for women). After further adjustment of the BMI, the risk of metabolic syndrome still increased slightly for men but not for women in increasing leptin categories. This association of leptin levels and metabolic syndrome did not change after stratification into obese and nonobese weight status. Serum leptin is associated with metabolic syndrome in Korean populations independent of body mass index. Thus, the reduction of circulating leptin may confer cardiovascular and metabolic protective effects regardless of weight status.

Topics: Abdominal Fat; Adult; Body Mass Index; Female; Humans; Hyperglycemia; Hypertension; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Obesity; Odds Ratio; Republic of Korea; Triglycerides; Waist Circumference

The leptin-deficient ob/ob mice are insulin resistant and obese. However, the control of blood pressure in this model is not well defined. The goal of this study was to evaluate the role of leptin and of the renin-angiotensin system in the cardiovascular abnormalities observed in obesity using a model lacking leptin. To this purpose, we measured blood pressure in ob/ob and control animals by radiotelemetry combined with fast Fourier transformation before and after both leptin and enalapril treatment. Autonomic function was assessed pharmacologically. Blood pressure during daytime was slightly higher in the ob/ob compared to control mice, while no difference in heart rate was observed. Blood pressure response to trimetaphane and heart rate response to metoprolol were greater in ob/ob mice than in control littermates indicating an activated sympathetic nervous system. Heart rate response to atropine was attenuated. Baroreflex sensitivity and heart rate variability were blunted in ob/ob mice, while low frequency of systolic blood pressure variability was found increased. Chronic leptin replacement reduced blood pressure and reversed the impaired autonomic function observed in ob/ob mice. Inhibition of angiotensin-converting enzyme by enalapril treatment had similar effects, prior to the loss of weight. These findings suggest that the renin-angiotensin system is involved in the autonomic dysfunction caused by the lack of leptin in ob/ob mice and support a role of this interplay in the pathogenesis of obesity, hypertension, and metabolic syndrome.

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Baroreflex; Disease Models, Animal; Fourier Analysis; Hypertension; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity; Peptidyl-Dipeptidase A; Renin-Angiotensin System

Leptin and adiponectin are hormones secreted by adipose tissue, and both hormones are candidate intermediaries between adipose tissue and overweight-related diseases. So far, no prospective study has been published where the independent effects of these two hormones on the development of hypertension have been directly compared. The objective of this study was to investigate the relationships between plasma levels of leptin and adiponectin and new-onset hypertension in the Copenhagen City Heart Study (CCHS).. In a prospective study design, we examined new-onset hypertension in 620 women and 300 men who were normotensive in the third CCHS examination, which was performed in 1991-1994.. Between the third and the fourth CCHS examination, which was performed in 2001-2003, 254 had developed hypertension, defined as systolic blood pressure (SBP) > or = 140 mm Hg, or diastolic blood pressure (DBP) > or = 90 mm Hg, or use of antihypertensive medication. Using logistic regression analysis, adjusting for age, sex, estimated glomerular filtration rate, triglycerides, high-density lipoprotein cholesterol (HDL-C), fibrinogen, and glucose, and with leptin and adiponectin included in the same model, leptin was significantly associated with new-onset hypertension with an odds ratio (95% confidence interval) of 1.28 (1.08-1.53; P < 0.005) for 1 s.d. higher level of log-transformed leptin, whereas adiponectin was not significantly associated with new-onset hypertension having an odds ratio of 1.02 (0.84-1.24; P = 0.83) for 1 s.d. higher level of log-transformed adiponectin.. In the CCHS, leptin, but not adiponectin, was a significant independent predictor of new-onset hypertension.

Topics: Adiponectin; Adult; Biomarkers; Denmark; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Prognosis

In our previous study, moderate increases in plasma leptin levels achieved via administration of recombinant adenovirus containing the rat leptin cDNA were shown to correct the abnormal metabolic profile in rats with diet-induced obesity, suggesting that these animals had developed resistance to the metabolic effects of leptin, which could be reversed by leptin gene over-expression. However, the effect of this therapeutic strategy on blood pressure was not investigated. The present study aimed to determine whether a moderate increase of endogenous plasma leptin levels affected arterial blood pressure in rats with diet-induced obesity and hypertension. The major finding from the present study was that the natural rise in plasma leptin with weight-gain is insufficient to counterbalance high blood pressure associated with obesity, additional increases of circulating leptin levels with adenoviral leptin gene therapy led to normalisation of blood pressure in high-fat diet-induced obese and hypertensive rats. Mechanistically, the reduction of blood pressure by leptin in obese rats was likely independent of alpha-adrenergic and acetylcholinergic receptor mediation. This is the first study to demonstrate that further increases in circulating leptin levels by leptin gene transfer during obesity could reduce blood pressure.

Topics: Adenoviridae; Animals; Dietary Fats; Gene Transfer Techniques; Genetic Therapy; Hypertension; Leptin; Male; Obesity; Rats; Rats, Wistar

The importance of hypertension treatment has expanded beyond blood pressure management to include additional risk factors, mainly diabetes. It was considered of interest to test the effect of telmisartan, an angiotensin receptor 1 antagonist and peroxisome proliferator activator receptor-gamma partial agonist, on Cohen-Rosenthal diabetic hypertensive nonobese (CRDH) rats, a unique model combining both pathologies. Its effect was examined on fat-derived and inflammatory agents in CRDH. To determine the extent of the drug's peroxisome proliferator activator receptor-gamma modulating beneficial metabolic actions, results were compared with those obtained with valsartan and rosiglitazone in CRDH and Cohen diabetic rat (CDR). Telmisartan and valsartan were given in drinking water at 3 and 12 mg/kg/d, whereas rosiglitazone (3 mg/kg/d) was given as food admixture for a period of 5 months. Blood pressure, glucose, insulin, adiponectin, leptin, and tumor necrosis factor alpha were examined. Telmisartan and valsartan significantly (P < .01) reduced blood pressure, whereas telmisartan and rosiglitazone considerably reduced blood glucose levels to normoglycemic levels (P < .01) in these 2 strains. Insulin levels were not affected by telmisartan and valsartan but were slightly reduced by rosiglitazone in CDR. In contrast to valsartan, adiponectin was significantly (60%, P < .01) increased by telmisartan in both CDR and CRDH, whereas rosiglitazone induced a 60% and 180% increase in CRDH and CDR animals, respectively, on day 30 of treatment. Co-treatment with GW9662 averted telmisartan-induced rise of adiponectin. Tumor necrosis factor alpha declined in telmisartan-treated rats, less so with rosiglitazone, but not valsartan. Telmisartan also induced downsizing of epididymal adipocytes compared with valsartan. Leptin levels were significantly increased by valsartan (P < .05) but reduced by telmisartan and rosiglitazone. The telmisartan-induced increase in adiponectin was most probably associated with a decrease in glucose and tumor necrosis factor alpha levels. Therefore, in addition to its hypotensive effect, telmisartan demonstrated beneficial thiazolidinedione-like effects.

Topics: Adiponectin; Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Benzoates; Blood Pressure; Humans; Hyperglycemia; Hypertension; Insulin; Insulin Resistance; Leptin; PPAR gamma; Rats; Rats, Inbred SHR; Rosiglitazone; Telmisartan; Thiazolidinediones; Tumor Necrosis Factor-alpha; Weight Gain

Leptin is a circulating adipocyte-derived hormone that influences blood pressure (BP) and metabolism. This study was designed to define the possible role of leptin in regulation of the atrial natriuretic peptide (ANP) system using acute and chronic experiments. Intravenous infusion of rat leptin (250 microg/kg injection plus 2 microg.kg(-1).min(-1) for 20 min) into Sprague-Dawley rats increased BP by 25 mmHg and decreased plasma level of ANP from 80.3 +/- 3.45 to 51.8 +/- 3.3 pg/ml. Reserpinization attenuated the rise in BP, but not the reduction of plasma ANP during leptin infusion. N(omega)-nitro-l-arginine methyl ester prevented the effects of leptin on the reduction of ANP level. In hyperleptinemic rats that received adenovirus containing rat leptin cDNA (AdCMV-leptin), BP increased during first 2 days and then recovered to control value. Plasma concentration of ANP and expression of ANP mRNA, but not of atrial ANP, in hyperleptinemic rats were lower than in the control groups on the first and second week after administration of AdCMV-leptin. These effects were not observed by the pretreatment with N(omega)-nitro-l-arginine methyl ester. No differences in renal function and ANP receptor density in the kidney were found between hyperleptinemic and control rats. Basal ANP secretion and isoproterenol-induced suppression of ANP secretion from isolated, perfused atria of hyperleptinemic rats were not different from those of other control groups. These data suggest that leptin inhibits ANP secretion indirectly through nitric oxide without changing basal or isoproterenol-induced ANP secretion.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Carotid Arteries; Hypertension; Isoproterenol; Jugular Veins; Kidney; Leptin; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide; Rats; Rats, Sprague-Dawley; Reserpine; RNA, Messenger

Chronic kidney disease (CKD) is a significant public health problem that leads to end-stage renal disease (ESRD) with as many as 2 million people predicted to need therapy worldwide by 2010. Obesity is a risk factor for CKD and leptin, the obesity hormone, correlates with body fat mass and markers of renal function. A number of clinical and experimental studies have suggested a link between serum leptin and kidney disease. We hypothesised that variants in the leptin gene (LEP) may be associated with markers of CKD in indigenous black Africans.. Black South Africans of Xhosa (distinct cultural Bantu-speaking population) descent were recruited for the study and four common polymorphisms of the LEP (rs7799039, rs791620, rs2167270 and STS-U43653 [ENSSNP5824596]) were analysed for genotype and haplotype association with urine albumin-to-creatinine ratio (UACR), estimated glomerular filtration rate (eGFR), Serum creatinine (Scr) and serum leptin level. In one of the four single nucleotide polymorphisms (SNPs) we examined, an association with the renal phenotypes was observed. Hypertensive subjects with the T allele (CT genotype) of the ENSSNP5824596 SNP had a significantly higher eGFR (p = 0.0141), and significantly lower Scr (p = 0.0137). This was confirmed by haplotype analysis. Also, the haplotype GAAC had a modest effect on urine albumin-to-creatinine ratio in normotensive subjects (p = 0.0482).. These results suggest that genetic variations of the LEP may be associated with phenotypes that are markers of CKD in black Africans.

Topics: Adult; Albuminuria; Alleles; Base Sequence; Black People; Chronic Disease; Creatinine; Female; Gene Frequency; Genetic Predisposition to Disease; Genetic Variation; Genotype; Glomerular Filtration Rate; Haplotypes; Humans; Hypertension; Kidney Diseases; Leptin; Linkage Disequilibrium; Male; Middle Aged; Polymorphism, Single Nucleotide; South Africa

Leptin is associated with blood pressure (BP) in experimental and cross-sectional studies, but only one previous prospective study of middle-aged men has reported the association between leptin and incident hypertension. We examined the association of leptin levels with incident hypertension in a population-based study of older men and women.. Longitudinal cohort study.. Participants were 602 community-dwelling older adults with normal baseline BP levels who attended a research clinic visit between 1984 and 1987 and again 4.4 years later (mean age was 66.2 +/- 11.4; 60.6% were men; mean body mass index (BMI) 24.9 +/- 3.4 kg/m(2)).. Hypertension was defined as systolic BP > or =140 mmHg and/or diastolic BP > or =90 mmHg and/or antihypertensive drug treatment. Leptin was measured by radioimmunoassay.. After an average 4.4-year follow-up (minimum 2-maximum 7 years), 106 (17.6%) new cases of hypertension were identified. At baseline, participants who developed hypertension were older and had higher systolic BP and higher total cholesterol compared to participants who remained normotensive. Baseline serum leptin levels were higher in participants who developed hypertension compared to persistent normotensives [median (25th-75th range)] [8.8(5-16) vs 7(4-11) ng/ml, P = 0.002]. In logistic regression models, leptin (log-transformed) predicted incident hypertension before and after adjustments for baseline age, BMI, systolic BP, total cholesterol, medications, and previous cardiovascular disease (OR 1.75 95% CI 1.17-2.61, P = 0.006). This association persisted after exclusion of 45 obese participants.. Higher leptin levels were independently associated with increased odds of incident hypertension in older adults.

Topics: Adult; Aged; Aged, 80 and over; Diagnostic Techniques, Endocrine; Female; Humans; Hypertension; Incidence; Leptin; Male; Middle Aged; Prognosis

Topics: Humans; Hypertension; Leptin; Obesity; Sympathetic Nervous System

Primary aldosteronism (PA) has been recently associated with an unfavorable cardiometabolic profile. However, whether pro- and antiinflammatory adipokines levels can vary in PA is unknown.. We evaluated the circulating levels of resistin, leptin, and adiponectin, echocardiographic left ventricle (LV) parameters, and the prevalence of metabolic syndrome (SM) in subjects with PA.. Seventy-five subjects with established diagnosis of PA and 232 consecutive individuals with known or suspected hypertension were enrolled.. Plasma adipokine levels and echocardiographic parameters were calculated. Prevalence of SM was also estimated.. Among the 75 PA subjects, 37 patients were affected by aldosterone-producing adenoma and 38 by idiopathic hyperaldosteronism; 40 subjects were affected by essential hypertension (EH) and SM (EH SM+); 152 subjects were affected by EH without SM (EH SM-); and 40 subjects were normotensive (NT). Subjects with PA had the highest plasma resistin levels among the four groups (P < 0.01). Plasma resistin concentration was significantly higher in PA subjects when compared with EH SM+ individuals (P < 0.01) and EH SM- subjects (P < 0.01). PA subjects showed the higher LV mass and left atrium than EH individuals, irrespectively of the presence of SM (P < 0.01 for both). Plasma resistin levels was significantly correlated with ejection fraction and LV end-diastolic volume. The prevalence of SM was higher in PA subjects than in those with EH (25.4 vs. 20.3%).. Our data suggest that elevated aldosterone levels is associated with elevated circulating resistin levels and cardiac morphological changes independently of the presence of SM.

Topics: Adenoma; Adiponectin; Adult; Aged; Aldosterone; Biomarkers; Blood Glucose; Blood Pressure; C-Reactive Protein; Cholesterol; Echocardiography; Female; Heart Ventricles; Humans; Hyperaldosteronism; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Resistin; Young Adult

To explore the roles of hypertension and serum leptin in obstructive sleep apnea hypopnea syndrome (OSAHS).. Totally 60 patients with OSAHS (OSAHS group) and 40 age- and body mass index (BMI)-matched non-OSAHS individuals (non-OSAHS group) were enrolled in this study. The neck circumference (NC), waist/hip rate (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), leptin, fasting blood glucose (FBG), triglyceral (TG), cholesterol (Chol), and true insulin (TI) were measured before and after sleep . The correlations between hypertension/serum leptin level and OSAHS were analyzed.. The blood pressure(in the morning), especially DBP was significantly higher in OSAHS group than in non-OSAHS control group (89.75+/-2.04) mmHg vs. (81.63+/-1.91) mmHg, P<0.01. DBP in OSAHS group was positively correlated with serum leptin and apnea hypopnea index (AHI) (r=0.282, P<0.05; r=0.318, P<0.01). Logistic regression analysis showed that BMI (P=0.029), heart rate in the morning (P =0.030), and leptin (P=0.049) were independently correlated with the development of hypertension.. OSAHS may independently affect blood pressure, especially DBP, after waking up. BMIHR in the morning and serum leptin may be the independent correlates of hypertension.

Topics: Adult; Case-Control Studies; Humans; Hypertension; Leptin; Male; Middle Aged; Sleep Apnea, Obstructive

Topics: Animals; Blood Pressure; Cardiovascular Physiological Phenomena; Disease Models, Animal; Hypertension; Leptin; Melanocortins; Mice; Obesity; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Rats; Thyrotropin-Releasing Hormone

Omega-3 polyunsaturated fatty acid deficiency, particularly during the prenatal period, can cause hypertension in later life. This study examined the effect of different sources of alpha-linolenic acid (canola oil or flaxseed oil) in the prevention of hypertension and other metabolic symptoms induced by an omega-3 fatty acid-deficient diet. Dams were provided one of three experimental diets from 1 week before mating. Diets were either deficient (10% safflower oil-DEF) or sufficient (7% safflower oil+3% flaxseed oil-SUF-F; or 10% canola oil-SUF-C) in omega-3 fatty acids. The male offspring were continued on the maternal diet from weaning for the duration of the study. Body weight, ingestive behaviors, blood pressure, body composition, metabolic rate, plasma leptin and brain fatty acids were all assessed. The DEF animals were hypertensive at 24 weeks of age compared with SUF-F or SUF-C animals; this was not evident at 12 weeks. These results suggest that different sources of ALA are effective in preventing hypertension related to omega-3 fatty acid deficiency. However, there were other marked differences between the DEF and, in particular, the SUF-C phenotype including lowered body weight, adiposity, leptin and food intake in SUF-C animals. SUF-F animals also had lower, but less marked reductions in adiposity and leptin compared with DEF animals. The differences observed between DEF, SUF-F and SUF-C phenotypes indicate that body fat and leptin may be involved in omega-3 fatty acid deficiency hypertension.

Topics: alpha-Linolenic Acid; Animal Feed; Animals; Blood Pressure; Body Composition; Body Weight; Brain; Calorimetry; Deficiency Diseases; Energy Metabolism; Fatty Acids, Monounsaturated; Female; Heart Rate; Hypertension; Leptin; Linseed Oil; Male; Pregnancy; Prenatal Exposure Delayed Effects; Rapeseed Oil; Rats; Rats, Sprague-Dawley; Safflower Oil

Topics: Adiponectin; Biomarkers; Cohort Studies; Humans; Hypertension; Insulin Resistance; Leptin; Metabolic Syndrome; Sleep Apnea, Obstructive

The relationship between menopause and hypertension has been a topic of investigation for several years. In the pathogenesis of hypertension after menopause, metabolic disturbances play an important role.. To assess the relationship between adipocytokines and blood pressure, lipid and glucose metabolism in middle-aged perimenopausal women with essential hypertension.. The study included 192 women aged 40 to 60 years (mean age 51.73 +/- 1.82 years), 152 with mild and moderate essential hypertension and 40 normotensive age-matched controls. The diagnosis of menopause was based on the data from medical records and confirmed by serum concentrations of the FSH. The study population was stratified according to the menopausal status into four subgroups (normotensive pre- and postmenopausal, and hypertensive pre- and postmenopausal patients). In all subjects anthropometrical measurements and 24-hour ambulatory blood pressure monitoring were performed. Serum levels of leptin, adiponectin and resistin were measured using immunochemical assays. Fasting blood samples were taken for glucose, insulin and serum lipids concentration.. Postmenopausal women did not differ from premenopausal in respect to mean arterial pressure (normotensive 85.2 +/- +/- 5.6 vs 84.4 +/- 4.9 mm Hg; hypertensive 99.5 +/- 5.9 vs 98.8 +/- 5.3 mm Hg). Menopause had no effects on glucose metabolism. Total cholesterol and LDL cholesterol were significantly higher in postmenopausal women. In multiple regression analysis, the strongest predictors of hypertension were waist circumference and serum leptin concentration. Adiponectin and resistin levels were not associated with blood pressure values.. In hypertensive postmenopausal females increased leptin level may play an important role in the pathogenesis of hypertension, independent of body mass index. Menopause per se does not affect blood pressure values. The influence of menopause on serum lipids may modulate the cardiovascular risk profile in postmenopausal females.

Topics: Adipokines; Adiponectin; Adult; Blood Glucose; Blood Pressure Monitoring, Ambulatory; Cholesterol; Cholesterol, LDL; Female; Humans; Hypertension; Leptin; Lipid Metabolism; Middle Aged; Perimenopause; Resistin

The Spontaneously Diabetic Torii-Lepr(fa) (SDT-fa/fa) rat, a new model of obese type 2 diabetes, shows obesity, hyperglycemia, and hyperlipidemia from 6 weeks of age. Diabetic complications such as nephropathy and cataract are observed with aging; however, blood pressure change with age has not previously been examined. In this study, blood pressure was periodically measured and the change was investigated. Blood pressure in male SDT-fa/fa rats was elevated at 8, 16, and 24 weeks of age, whereas the heart rate was not changed. In addition to hyperglycemia, hyperlipidemia, and proteinuria, hyperleptinemia and increased urine angiotensinogen were observed in SDT-fa/fa rats. Blood pressure and heart rate in the male original SDT (SDT-+/+) rat did not significantly change. In conclusion, the SDT-fa/fa rat is a promising model, showing significant hypertension with diabetes mellitus.

Topics: Angiotensinogen; Animals; Blood Pressure; Diabetes Mellitus, Type 2; Disease Models, Animal; Heart Rate; Hyperglycemia; Hyperlipidemias; Hypertension; Leptin; Male; Obesity; Proteinuria; Rats; Rats, Sprague-Dawley

Topics: Adult; Black or African American; Blood Pressure; Body Mass Index; Female; Humans; Hypertension; Leptin; Male; Mexican Americans; Middle Aged; Odds Ratio; Sex Factors; United States; White People

Leptin is an adipose tissue-derived hormone shown to be related to metabolic, inflammatory, and hemostatic factors involved in hypertension development. Animal studies suggest that higher leptin levels may activate the sympathetic nervous system and cause elevations in blood pressure (BP). However, few studies have examined the association between leptin and hypertension in humans. Also it is not clear whether this association is present among women as well as men. Therefore, we examined the association between plasma leptin levels and hypertension in a representative sample of US adults. We examined the third National Health and Nutrition Examination Survey participants >20 years of age (n=5599; 54.7% women). Plasma leptin levels were categorized into quartiles (women: <7.68, 7.68 to 13.18, 13.19 to 21.70, >21.70 fg/L; men: <2.64, 2.64 to 4.36, 4.37 to 7.12, >7.12 fg/L). Hypertension was defined as BP-reducing medication use or having systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg. We found that higher plasma leptin levels were positively associated with hypertension after adjusting for age, sex, race/ethnicity, education, smoking, alcohol intake, body mass index, diabetes mellitus, serum cholesterol, and C-reactive protein. Compared with quartile 1 of leptin (referent), the odds ratio (95% CI) of hypertension associated with quartile 4 was 1.89 (1.24 to 2.09; P for trend=0.0036). Subgroup analyses examining the relation between leptin and hypertension by sex and body mass index categories also showed a consistent positive association. In conclusion, higher plasma leptin levels are associated with hypertension both among women as well as men in a representative sample of US adults.

Topics: Adult; Black or African American; Blood Pressure; Body Mass Index; C-Reactive Protein; Cholesterol; Diabetes Mellitus; Educational Status; Fasting; Female; Humans; Hypertension; Leptin; Logistic Models; Male; Mexican Americans; Middle Aged; Multivariate Analysis; Nutrition Surveys; Odds Ratio; Sex Factors; United States; White People

To study of the contribution of obesity to renal lesion in patients with type 2 diabetes mellitus (T2DM).. One hundred and fifty-four patients (62 males and 92 females) with T2DM (mean age 58 +/- 8 years) were examined. The study excluded patients with significant stages of diabetic nephropathy (glomerular filtration rate (GFR) < 60 ml/min; proteinuria more than 2 g/day). Anthropometric indicators, such as body mass index (BMI), were estimated. The serum levels of creatinine, uric acid (UA), lipid composition, and the adipose tissue hormones leptin and adiponectin were measured. Renal lesion was evaluated from GFR and urine albumin excretion level. Groups of patients with a less and more than 5-year history and subgroups of a MBI of less and more than 30 kg/mi were identified.. In patients with a more than 5-year history of T2DM, the detection rate of microalbuminuria and proteinuria increased as obesity progressed. This regularity was not found in those with a less than 5-year history of T2DM. Diabetic patients with a BMI of > 30 kg/m2 were more frequently found to have intrarenal hemodynamic disorders (hyperfiltration) elevated blood pressure, increased UA, and decreased high-density lipoproteins, as compared with those with a BMI of < 30 kg/m2. With a higher BMI, leptin levels increased; its highest values were found in a group of patients with proteinuria. Hypoadiponectinemia was detected in most patients with T2DM. Adiponectin was decreased in early-stage nephropathy; its increase was further increased.. There was a greater prevalence of renal lesion in obese (BMI > 30 kg/m2) patients with a more than 5-year history of T2DM than in non-obese patients. Obesity has an impact on renal function due to its hemodynamic, metabolic, and hormonal effects.

Topics: Adiponectin; Adult; Aged; Anthropometry; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Female; Hemodynamics; Humans; Hypertension; Kidney Function Tests; Leptin; Male; Middle Aged; Obesity; Risk Factors; Severity of Illness Index

Little is known about the impact of having one cardiovascular (CV) risk factor on the levels of other CV risk factors in the general adolescent population. We hypothesized that when adolescents have one CV risk factor, the levels of other CV risk factors worsen simultaneously.. Subjects consisted of 1,257 healthy adolescent volunteers (549 males and 708 females) aged 15-18 years. Abdominal obesity, hypertension, raised triglyceride levels, decreased HDL-cholesterol levels and hyperglycemia were used as CV risk factors. Homeostasis assessment of insulin resistance (HOMA-IR) was used as a surrogate marker of insulin resistance. Levels of four biomarkers, leptin, adiponectin, high-sensitive C-reactive protein, and desacyl-ghrelin, were also determined. Cut-offs for gender-specific individual CV risk factor levels were based on the 90th (or 10th) percentile values of the subjects in the present study.. The levels of all CV risk factors and HOMA-IR significantly and simultaneously worsened when adolescents had one CV risk factor in both genders. Having any one CV risk factor indicated the development of other CV risk factors in adolescents; in particular, we found that the development of abdominal obesity in male subjects had a harmful effect on the levels of other CV risk factors and was associated with the worsening of all four biomarkers examined.. It is important to determine the presence or absence of these CV risk factors before and/or during adolescence, because having one CV risk factor indicates the start of an accumulation of CV risk factors in the general adolescent population.

Topics: Adiponectin; Adolescent; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Cholesterol, HDL; Female; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Male; Obesity; Risk Factors; Triglycerides

The present study was aimed at evaluating the correlation between leptin and hypertension in normal and obese hypertensive pre- (Pre-M) and postmenopausal (Post-M) women of Jalandhar city (Punjab, India).. For the present study, 78 Pre-M and Post-M women were recruited in four categories as follows: i) normal normotensive, ii) obese normotensive, iii) normal hypertensive, and iv) obese hypertensive. Body mass index was considered as the index of obesity. Guidelines given by JNC-VII were followed for the assessment of hypertension. Leptin was assayed by sandwich ELISA, and estradiol (E(2)) was assayed by competitive ELISA.. Leptin level was found to be significantly higher in normal Pre-M women (P<0.02) than that of normal Post-M women. Obese subjects had significantly higher leptin level (P<0.001) than the normal women. In the case of hypertensive subjects, leptin level was significantly higher than that of normotensive counterparts. E(2) level was found significantly lower in Post-M women (P<0.001) than that of Pre-M women as well as in hypertensive women than that of normotensive subjects. A positive correlation was observed between blood pressure (BP) and leptin, but significant association was observed in hypertensive normal and obese Pre-M and Post-M women only.. It is concluded from the present findings that leptin contributes to the regulation of BP in hypertensive normal as well as in the obese Pre-M and Post-M women. So, leptin may be a regulator of BP in hypertensive women independent of the degree of obesity and the menopausal status.

Topics: Adult; Cross-Sectional Studies; Female; Humans; Hypertension; India; Leptin; Menopause; Middle Aged; Obesity; Postmenopause; Premenopause

to examine the associations of several markers of adiposity and a wide range of cardiovascular risk factors and biomarkers in pre-pubertal children.. four measures of adiposity,body mass index (BMI), waist circumference, dual-energy X-ray absorptiometry (DXA)-determined fat mass, and leptin concentration, were available in up to 7589 children aged 8.8-11.7 (9.9 mean) years from the Avon Longitudinal Study of Parents and Children (ALSPAC). Thirteen per cent of boys and 18.8% of girls were overweight, and 5.3% of boys and 5% of girls were obese. Body mass index was highly correlated with waist circumference (r = 0.91), DXA fat mass (r = 0.87), and leptin concentration (r = 0.75), and all had similar associations with cardiovascular risk factors. A 1 kg/m(2) greater BMI was associated with 1.4 mmHg (95% CI 1.25-1.44) higher systolic blood pressure (BP). In 5002 children, a 1 kg/m(2) greater BMI was associated with a 0.05 mmol/L (95% CI 0.036-0.055) higher non-high-density lipoprotein (HDL) cholesterol and 0.03 mmol/L (95% CI -0.034 to -0.025) lower HDL cholesterol. There were also graded associations with apolipoproteins A1 and B, interleukin-6, and C-reactive protein. Comparing children who were obese with those who were normal weight, the odds ratio for hypertension was 10.7 (95% CI 7.2-15.9) for boys and 13.5 (95% CI 9.4-19.5) for girls.. in pre-pubertal UK children, overweight/obesity is common and has broadly similar associations with BP, HDL cholesterol, and non-HDL cholesterol to those observed in adults. Future research should evaluate whether effective interventions to maintain healthy weight in childhood could have important benefits for adult cardiovascular risk.

Topics: Absorptiometry, Photon; Adipose Tissue; Adiposity; Body Mass Index; Child; Cholesterol, LDL; Female; Humans; Hypertension; Hypertriglyceridemia; Leptin; Longitudinal Studies; Male; Obesity; Overweight; Risk Factors; Waist Circumference

Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high- or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or "junk food" diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance.

Topics: Adiposity; Age Factors; Aging; Animal Nutritional Physiological Phenomena; Animals; Behavior, Animal; Blood Pressure; Body Weight; Conditioning, Operant; Dietary Fats; Disease Models, Animal; Feeding Behavior; Female; Hybridization, Genetic; Hyperphagia; Hypertension; Insulin; Lactation; Leptin; Male; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Motivation; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred SHR; Rats, Wistar; Reward; Weaning

Leptin increases sympathetic activity, possibly contributing to hypertension in obese subjects. Hypertension increases cardiovascular mortality, with nighttime (sleep) blood pressure having a substantial prognostic value. We measured blood pressure in male leptin-deficient obese mice (ob/ob; n=7) and their lean wild-type littermates (+/+; n=11) during wakefulness, non-rapid-eye-movement sleep, and rapid-eye-movement sleep to investigate whether, in the absence of leptin, derangements of blood pressure are still associated with obesity and depend on the wake-sleep state. Mice were implanted with a telemetric pressure transducer and electrodes for discriminating wake-sleep states. Mean blood pressure was significantly higher in ob/ob than in +/+ mice during wakefulness (7.3+/-2.6 mm Hg) and non-rapid-eye-movement sleep (6.7+/-2.8 mm Hg) but not during rapid-eye-movement sleep (2.6+/-2.6 mm Hg). In ob/ob and +/+ mice, mean blood pressure was substantially higher during wakefulness than during non-rapid-eye-movement sleep. On passing from non-rapid-eye-movement sleep to rapid-eye-movement sleep, mean blood pressure decreased significantly in ob/ob but not in +/+ mice. The time spent during wakefulness was lower in ob/ob than in +/+ mice during the dark (active) period, whereas the opposite occurred during the light (rest) period. Consequently, mean blood pressure was significantly higher in ob/ob than in +/+ mice during the light (8.2+/-2.4 mm Hg) but not during the dark (3.0+/-2.9 mm Hg) period. These data suggest that, in the absence of leptin, obesity may entail hypertensive derangements of blood pressure, which are substantially modulated by the cardiovascular effects of the wake-sleep states.

Topics: Animals; Blood Pressure; Codon, Nonsense; Disease Models, Animal; Hypertension; Leptin; Male; Mice; Mice, Mutant Strains; Obesity; Sleep; Sleep, REM; Wakefulness

Abnormal adipocyte function is implicated in the coalition of multiple cardiovascular risk factors, where aberrant circulating levels of the adipose-derived hormones adiponectin, leptin, and tumour necrosis factor (TNF) alpha may provide the putative link between hypertension and increased cardiovascular risk. The pragmatic utility of these 'adipocytokines' in the clinical setting of hypertension is unclear, and we hypothesized a relationship of circulating adipocytokines to hypertension, and associated cardiovascular morbidity.. Using a cross-sectional approach, we measured plasma adipocytokines in 278 'high-risk' treated hypertensive participants of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) study (mean (SD) age 62.9 (7.7) years), who were compared to 54 newly diagnosed untreated hypertensives (61.3 (10.9) years) and 55 healthy controls (48.3 (12.3) years).. Levels of all three adipocytokines were lower amongst treated hypertensives compared to newly diagnosed hypertensives and healthy controls (P<0.001 for leptin and adiponectin), and varied with gender, co-morbidities (e.g. diabetes, cardiovascular disease (CVD), left ventricular hypertrophy) and by treatments (e.g. statins and beta-blockade). Levels of adiponectin (P<0.001) and leptin (P=0.02) rose in an ordinal fashion with increasing hypertension severity (grade). Levels of leptin were associated with diastolic blood pressure in a positive fashion (P<0.001).. While hypertension affects adipocytokine levels, the clinical interpretation of circulating levels in hypertension is confounded by a range of factors. The positive relation between leptin and adiponectin with hypertension severity may reflect an underlying adaptive response that is attenuated during pharmacological hypertension management.

Topics: Adiponectin; Aged; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Regression Analysis; Risk Factors; Tumor Necrosis Factor-alpha

Leptin is a key neuroendocrine hormone regulating food intake, metabolism, and fat accumulation, and it may also affect blood pressure and contribute to hypertension through sympathetic activation in the vasculature or at the renal level. Although previous studies have shown that the distribution of leptin is significantly different between males and females, as is the risk of hypertension between males and females, results regarding the role of leptin in the gender-specific regulation of blood pressure are controversial. Thus, we performed family-based association analyses in the National Heart, Lung, and Blood Institute Family Heart Study to test the hypothesis that LEPTIN gene variants and the plasma leptin level influence variability in blood pressure and the risk of hypertension differently by gender. We identified significant associations between LEPTIN single nucleotide polymorphisms with blood pressure and hypertension, but in postmenopausal women only. We also identified significant associations between plasma leptin levels and both blood pressure and hypertension in women. The current study supports a role for LEPTIN and plasma leptin levels in blood pressure regulation in women. It also provides insight into the gender differences in hypertension, as well as the differential distribution and activity of leptin in men and women.

Topics: Adult; Blood Pressure; Female; Haplotypes; Humans; Hypertension; Leptin; Male; Middle Aged; National Heart, Lung, and Blood Institute (U.S.); Phenotype; Polymorphism, Single Nucleotide; Promoter Regions, Genetic; Sex Characteristics; United States

This study assessed in obese Brazilians subjects whether a common variant of leptin gene, -2548G>A, is associated with blood pressure changes.. A total of 140 subjects, 99 women; mean age of 45.2 +/- 12.4 years; body mass index (BMI) = 38.5 +/- 8.0 kg/m2 were included. Blood pressure was recorded using Dinamap 1846 (Critikon, Tampa, FL). Molecular analysis was made by use of PCR and restriction fragment-length polymorphism analysis. Plasma insulin and leptin concentrations were determined by radioimmunoassay.. AA homozygotes, in comparison with the G-allele carriers, showed significant lower levels of systolic, diastolic, and mean arterial pressure (120 +/- 10 vs. 132 +/- 17 mm Hg, P = 0.01; 75 +/- 6 vs. 84 +/- 12 mm Hg, P = 0.009; 92 +/- 7 vs. 100 +/- 12 mm Hg, P = 0.007, respectively). The differences in blood pressure remained significant after adjusting for the influence of gender, age, obesity, and body fat distribution as well as for leptin, insulin, and homeostasis model assessment of insulin resistance. A stepwise regression analysis confirmed that the LEP AA genotype independently predicted blood pressure changes. On the other hand, in GG homozygotes, insulinemia showed a significant association with blood pressure values. This suggests that common LEP genotype carriers exhibiting high insulin levels, reflecting an insulin-resistant state, were particularly prone to higher blood pressure levels.. Our results showing that higher blood pressure levels were found with the most prevalent -2548G>A genotype, whereas patients with the AA genotype seemed to be protected from hypertension, indicate that the -2548G>A polymorphism of LEP appears to be an important mediator of obesity hypertension.

Topics: Adolescent; Adult; Aged; Blood Pressure; Female; Humans; Hypertension; Leptin; Linear Models; Male; Middle Aged; Obesity

Epidemiologic data suggest an association between obesity and depression, however findings vary considerably across different studies. Both depression and obesity are disabling disorders associated with loss over appetite control, influenced by genetic and environmental factors and are risk factors for diseases like hypertension, cardiovascular disorders, etc. This study attempts to establish a link between the symptoms of depression, metabolic disorders, and obesity, to unravel the underlying association/s.. This exploratory case-control study comprises 133 clinically diagnosed depressed individuals and 136 age matched controls. DNA from all 269 subjects was genotyped for D7S1875 repeat polymorphism in the promoter region of Leptin (LEP) gene using polymerase chain reaction.. Frequency of the shorter allele of D7S1875 (<208 bp) was 0.73 in the depressive group versus 0.67 in the control group (P=.01). Cases homozygous for D7S1875> or =208 bp alleles had significantly higher value of systolic (130 versus 122; P<.009) and diastolic (85.4 versus 81; P=.01) blood pressure (SBP and DBP) than the individuals homozygous for<208 bp allele. A similar trend was observed for SBP (127.8 versus 123.6; P=.03) among controls homozygous for the longer or the shorter allele. Thus, the LEP gene appears to be an important genetic determinant for susceptibility to depression in the Indian population (OR=1.4913, 95% CI=1.0334-2.1522; P=.04).. Our findings suggest that LEP gene variants could be related to depression and associated co-morbidities such as hypertension.

Topics: Adult; Alleles; Blood Pressure; Body Mass Index; Case-Control Studies; Depressive Disorder; Female; Gene Frequency; Genetic Carrier Screening; Genetic Predisposition to Disease; Genotype; Homozygote; Humans; Hypertension; India; Leptin; Male; Middle Aged; Obesity; Polymerase Chain Reaction; Polymorphism, Genetic; Promoter Regions, Genetic

Topics: Blood Pressure; Female; Humans; Hypertension; Leptin; Male; Obesity

The aim of the study was to investigate whether diverse clinical blood pressure phenotypes are associated with free leptin surrogates, as reflected by plasma leptin, human soluble leptin receptor, and their ratio (ie, free leptin index) in nonobese normoglycemic subjects. Three separate clinic blood pressure measurements and ambulatory blood pressure monitoring were implemented to divide 494 subjects (aged 44+/-5 years; 272 men; body mass index: <30 kg/m(2)) into hypertensives (n=166), white-coat hypertensives (n=82), masked hypertensives (n=66), and normotensives (n=180). Participants underwent echocardiography, while, from fasting venous blood samples, metabolic profile, plasma leptin, and its receptor levels were assessed. Hypertensives and masked hypertensives demonstrated higher levels of log (10)(leptin) and log (10)(free leptin index), as well as lower levels of log (10)(human soluble leptin receptor) with respect to normotensives. White-coat hypertensives had similar free leptin surrogates compared with normotensives. Younger age, 24-hour systolic and diastolic blood pressures, 24-hour heart rate, and left ventricle mass index were common correlates of free leptin surrogates. After adjustment for confounders, masked hypertensive and hypertensive with respect to normotensive phenotype were associated with log (10)(leptin) with odds ratios (95% CIs) of 1.31 (1.12 to 3.80) and 1.26 (1.09 to 2.24), respectively, log (10)(human soluble leptin receptor) with 0.65 (0.53 to 0.78) and 0.69 (0.57 to 0.84), respectively, and log (10)(free leptin index) with 2.46 (1.32 to 7.23) and 1.84 (1.26 to 3.73), respectively (P<0.05 for all of the cases). Free leptin surrogates are associated with masked hypertension in nonobese normoglycemic subjects. Free leptin is almost equally increased in masked and sustained hypertension, suggesting a similar leptin-related vascular impairment.

Topics: Adult; Analysis of Variance; Biomarkers; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Body Mass Index; Cross-Sectional Studies; Echocardiography, Doppler; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Leptin; Linear Models; Logistic Models; Male; Middle Aged; Multivariate Analysis; Probability; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Ventricular Function, Left

Chemerin is a recently discovered adipokine that regulates adipocyte differentiation and modulates chemotaxis and activation of dendritic cells and macrophages. Given the convergence of adipocyte and macrophage function, chemerin may provide an interesting link between obesity, inflammation and atherosclerosis in humans. We sought to examine the relationship of i) chemerin and markers of inflammation, ii) chemerin and components of the metabolic syndrome, and iii) chemerin and coronary atherosclerotic plaque burden and morphology.. Serum chemerin levels were determined in 303 patients with stable typical or atypical chest pain who underwent dual-source multi-slice CT-angiography to exclude coronary artery stenosis. Atherosclerotic plaques were classified as calcified, mixed, or non-calcified.. Chemerin levels were highly correlated with high sensitivity C-reactive protein (r=0.44, P<0.0001), interleukin-6 (r=0.18, P=0.002), tumor necrosis factor-alpha (r=0.24, P<0.0001), resistin (r=0.28, P<0.0001), and leptin (r=0.36, P<0.0001) concentrations. Furthermore, chemerin was associated with components of the metabolic syndrome including body mass index (r=0.23, P=0.0002), triglycerides (r=0.29, P<0.0001), HDL-cholesterol (r=-0.18, P=0.003), and hypertension (P<0.0001). In bivariate analysis, chemerin levels were weakly correlated with coronary plaque burden (r=0.16, P=0.006) and the number of non-calcified plaques (r=0.14, P=0.02). These associations, however, were lost after adjusting for established cardiovascular risk factors (odds ratio, OR 1.17, 95% confidence interval (CI) 0.97-1.41, P=0.11 for coronary plaque burden; OR 1.06, 95% CI 0.96-1.17, P=0.22 for non-calcified plaques).. Chemerin is strongly associated with markers of inflammation and components of the metabolic syndrome. However, chemerin does not predict coronary atherosclerosis.

Topics: Aged; C-Reactive Protein; Chemokines; Cholesterol; Cohort Studies; Coronary Artery Disease; Female; Humans; Hypertension; Inflammation; Intercellular Signaling Peptides and Proteins; Interleukin-6; Leptin; Male; Metabolic Syndrome; Middle Aged; Regression Analysis; Resistin; Triglycerides; Tumor Necrosis Factor-alpha

To determine whether blood pressure (BP)-LVM relationships depend in-part on the influence of an excess adiposity and whether this translates into a greater effect of hypertension on LVM in obese as compared with lean people.. In 399 randomly recruited participants from a general population with a high prevalence of excess adiposity ( approximately 68%), we assessed whether the relationships between conventional blood pressure (BP) and LVM indexed for height (LVMI) (determined from echocardiography) are influenced by adiposity. We confirmed these outcomes using 24-h ambulatory measurements in 297 participants; and carotid-femoral pulse wave velocity (PWV) (applanation tonometry) in 328 participants and from plasma leptin concentrations, we assessed whether leptin could mediate this effect.. After adjustments for appropriate confounders, including the individual terms for adiposity and BP, interactions between adiposity indices (either waist circumference or the mean of subscapular and triceps skin-fold thickness) and either conventional systolic BP (SBP), 24-h SBP, PWV, conventional pulse pressure (PP), or 24-h PP were independently associated with LVMI (P < 0.001 for interactions). The adiposity index-haemodynamic interaction translated into a steeper slope of the BP-LVMI and PWV-LVMI relations in obese as compared with lean participants. Every one SD increase in conventional SBP ( approximately 22 mmHg) was associated with a 1.61 g/m increase in LVMI in participants with a normal waist circumference, in comparison to a 5.24 g/m increase in LVMI in those with an increased waist circumference (P < 0.0001). Furthermore, the adiposity index-haemodynamic interaction resulted in an increased LVMI in never-treated hypertensives with central obesity (LVMI, normotensives = 45.6 g/m, hypertensives = 51.0 g/m, P < 0.02), but not in participants with a normal waist circumference (LVMI, normotensives = 43.4 g/m, hypertensives = 45.0 g/m). Significant plasma leptin concentration-haemodynamic interactions were also associated with LVMI independent of confounders and adiposity indices, an effect that translated into a steeper slope of the haemodynamic factor-LVMI relations in participants with a plasma leptin concentration above as compared with those below the median for the group.. Adiposity-induced increases in LVM reflect an enhanced effect of BP on LV growth, an effect that may be mediated by leptin. This translates into an impact of never-treated hypertension on LVMI in centrally obese, but not in lean people in groups of African descent in South Africa.

Topics: Adiposity; Adult; Blood Pressure; Cross-Sectional Studies; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Male; Middle Aged; Obesity; Waist Circumference

To determine the role of neurohumoral dysfunction and overweight in a clinical course of arterial hypertension (AH).. 200 participants of the study aged 30-60 years with AH degree I-II with low, moderate and high overall cardiovascular risk and mean disease duration 11.1 +/- 9.5 years were examined for body mass index, levels of leptin, soluble leptin receptor, insulin, serotonin and adrenoreactivity.. Neurohumoral dysfunction correlated with body mass index. It manifested with elevation of insulin and leptin levels, sympathetic hyperactivity and a decrease of serotonin.. One of the mechanisms forming and sustaining AH in patients with overweight is leptin-dependent sympathetic hyperactivity while serotonin system activation is more important for patients with normal body weight. Hypertensive patients with obesity demonstrate insulin-dependent hyperleptinemia.

Topics: Adult; Case-Control Studies; Female; Humans; Hypertension; Insulin; Leptin; Male; Middle Aged; Overweight; Receptors, Leptin; Serotonin

To evaluate the impact of abdominal fat and insulin resistance on arterial hypertension of non-obese women.. Thirty-five non-obese women (NO), age 35-68 years were studied, and divided into two groups according to the presence of hypertension (BP >or= 140 x 90 mmHg) (HT = hypertensive; NT = normotensive). Leptin measurement and oral glucose tolerance test (OGTT) to assess insulin were performed in these patients. A CT-scan was used to evaluate visceral (VF) and subcutaneous abdominal fat (SCF). The Central fat distribution index (CDI) was proposed to evaluate the impact of subcutaneous abdominal fat on central fat distribution in hypertensive patients.. When compared to NT-NO (n = 17) group, HT-NO (n = 18) showed higher blood pressure levels (systolic and diastolic), greater VF area (84.40 +/- 55.70 versus 37.50 +/- 23.00 cm(2); p = 0.036), greater SCF area (174.30 +/- 83.00 versus 79.80 +/- 27.40 cm(2); p = 0.030), higher HOMAr index (1.59 +/- 0.72 versus 0.93 +/- 0.48 mmol*mU/L(2); p = 0.006), higher CDI index (12.67 +/- 7.04 versus 6.19 +/- 2.57 cm(2)/kg) and higher leptin level (19.1 +/- 9.6 versus 7.4 +/- 3.5 ng/mL; p = 0.028).. Arterial hypertension in non-obese women is associated with insulin resistance, central fat distribution and higher leptin levels.

Topics: Abdominal Fat; Adult; Aged; Body Mass Index; Cross-Sectional Studies; Electric Impedance; Female; Humans; Hypertension; Insulin Resistance; Leptin; Middle Aged; Obesity; Overweight; Subcutaneous Fat, Abdominal

The purpose of this study was to determine the long-term impact of obesity and related metabolic abnormalities in the absence and presence of hypertension on renal injury and salt-sensitivity of blood pressure. Markers of renal injury and blood pressure salt sensitivity were assessed in 52- to 55-wk-old normotensive melanocortin-4 receptor-deficient (MC4R-/-) mice and lean C57BL/6J wild-type (WT) mice and in 22-wk-old MC4R-/- and WT mice made hypertensive by N(G)-nitro-L-arginine methyl ester (L-NAME) in the drinking water for 8 wk. Old MC4R-/- mice were 60% heavier, hyperinsulinemic, and hyperleptinemic but had similar mean arterial pressure (MAP) as WT mice (115 +/- 2 and 117 +/- 2 mmHg) on normal salt diet (0.4% NaCl). A high-salt diet (4.0% NaCl) for 12 days did not raise MAP in obese or lean mice [DeltaMAP: MC4R (-/-) 4 +/- 2 mmHg; WT, 2 +/- 1 mmHg]. Obese MC4R-/- mice had 23% greater glomerular tuft area and moderately increased GFR compared with WT mice. Bowman's space, total glomerular area, mesangial matrix, urinary albumin excretion (UAE), renal TGF-beta and collagen expression were not significantly different between old MC4R-/- and WT mice. Renal lipid content was greater but renal macrophage count was markedly lower in MC4R-/- than WT mice. Mild increases in MAP during L-NAME treatment (approximately 16 mmHg) caused small, but greater, elevations in UAE, renal TGF-beta content, and macrophage infiltration in MC4R-/- compared with WT mice without significant changes in glomerular structure. Thus despite long-term obesity and multiple metabolic abnormalities, MC4R-/- mice have no evidence of renal injury or salt-sensitivity of blood pressure. These observations suggest that elevations in blood pressure may be necessary for obesity and related metabolic abnormalities to cause major renal injury or that MC4R-/- mice are protected from renal injury by mechanisms that are still unclear.

Topics: Age Factors; Albuminuria; Animals; Biomarkers; Blood Pressure; Body Weight; Disease Models, Animal; Glomerular Filtration Rate; Heart Rate; Hyperinsulinism; Hypertension; Kidney; Kidney Diseases; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Receptor, Melanocortin, Type 4; Sodium Chloride, Dietary

The aim of this study was to examine the effects of leptin on aortic rings with and without endothelium isolated from streptozotocin (STZ)-induced diabetic and control rats, and also in the presence of an inhibitor of nitric oxide synthase (NOS). Thoracic aortic rings from 5-week STZ-induced diabetic (50 mg/kg i.p.) and age-matched control Sprague-Dawley rats were mounted in isolated tissue baths. Concentration-response curves to leptin (0.1 pM-1 nM) were constructed under basal tone and after precontraction with 1 microM phenylephrine in the presence or absence of Nomega-nitro-L-arginine methyl ester (L-NAME, 10 microM). Leptin caused a concentration-dependent relaxation of precontracted endothelium-intact aortic rings from control and diabetic rats. Responses to leptin in diabetic aorta were significantly increased compared to those of controls (P < 0.05). EC(50) values for leptin were similar for aortic rings from diabetic and control rats (P > 0.05). L-NAME pretreatment caused complete inhibition of the relaxant responses to leptin in the control aortic rings, while it induced a reduction in these responses in the diabetic rings (P < 0.05). Leptin-induced relaxation was eliminated when the endothelium was denuded. Leptin had no effect on the basal tone of endothelium-intact or -denuded aortic rings from control rats. In diabetic rings, leptin elicited concentration-dependent contractions (P < 0.05). Removal of the endothelium significantly increased the contractile effect of leptin on basal tone in diabetic rings (P < 0.05). The results suggest that leptin may induce vasodilatation by endothelial mechanism(s) other than nitric oxide (NO) release from the endothelium in diabetic aortic rings. On the other hand, leptin causes contractile effects on the basal tone in aorta smooth muscle isolated from STZ-induced diabetic rats. The contractile effect of leptin on basal tone may contribute to the development of hypertension in diabetes.

Topics: Animals; Aorta; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Endothelium, Vascular; Hypertension; In Vitro Techniques; Leptin; Male; NG-Nitroarginine Methyl Ester; Rats; Rats, Sprague-Dawley; Streptozocin; Vasoconstriction

Obesity causes hypertension and sympathoactivation, a process proposed to be mediated by leptin. Protein tyrosine phosphatase 1B (PTP1B), a major new pharmaceutical target in the treatment of obesity and type II diabetes mellitus, constrains the metabolic actions of leptin, but the extent to which PTP1B regulates its cardiovascular effects is unclear. This study examined the hypothesis that PTP1B is a negative regulator of the cardiovascular effects of leptin.. PTP1B knockout mice had lower body fat but higher mean arterial pressure (116+/-5 versus 105+/-5 mm Hg, P<0.05) than controls. Leptin infusion produced a greater anorexic effect in PTP1B knockout mice and a marked increase in mean arterial pressure (135+/-5 mm Hg) in PTP1B knockout mice only. The decrease in mean arterial pressure in response to ganglionic blockade was higher in PTP1B knockout mice (-38+/-3% versus -29+/-3%, P<0.05), which suggests increased sympathetic tone. PTP1B deletion blunted mean arterial pressure responses to phenylephrine injection (55+/-10% versus 93+/-7%, P<0.05). Phenylephrine-induced aortic contraction was reduced in PTP1B knockout mice (57.7+/-9% versus 96.3+/-12% of KCl, P<0.05), consistent with desensitization to chronically elevated sympathetic tone. Furthermore, PTP1B deletion significantly reduced gene expression of 3 alpha(1)-adrenergic receptor subtypes, consistent with blunted constriction to phenylephrine.. These data indicate that PTP1B is a key regulator of the cardiovascular effects of leptin and that reduced vascular adrenergic reactivity provides a compensatory limit to the effects of leptin on mean arterial pressure.

Topics: Adrenergic alpha-Antagonists; Animals; Aorta; Blood Pressure; Hypertension; Leptin; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Obesity; Phenotype; Phenylephrine; Prazosin; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Receptors, Adrenergic, alpha-1; Stress, Physiological; Sympathetic Nervous System; Vasoconstriction; Vasoconstrictor Agents

A high-fat diet can increase adiposity, leptin secretion, and plasma fatty acid concentration. In hypertension, this scenario may accelerate cardiac hypertrophy and development of heart failure but could be protective by activating peroxisome proliferator-activated receptors and expression of mitochondrial oxidative enzymes. We assessed the effects of a high-fat diet on the development of left ventricular hypertrophy, remodeling, contractile dysfunction, and the activity of mitochondrial oxidative enzymes. Mice (n = 10-12/group) underwent transverse aortic constriction (TAC) or sham surgery and were fed either a low-fat diet (10% of energy intake as fat) or a high-fat diet (45% fat) for 6 wk. The high-fat diet increased adipose tissue mass and plasma leptin and insulin. Left ventricular mass and chamber size were unaffected by diet in sham animals. TAC increased left ventricular mass (approximately 70%) and end-systolic and end-diastolic areas (approximately 100% and approximately 45%, respectively) to the same extent in both dietary groups. The high-fat diet increased plasma free fatty acid concentration and prevented the decline in the activity of the mitochondrial enzymes medium chain acyl-coenzyme A dehydrogenase (MCAD) and citrate synthase that was observed with TAC animals on a low-fat diet. In conclusion, a high-fat diet did not worsen cardiac hypertrophy or left ventricular chamber enlargement despite increases in fat mass and insulin and leptin concentrations. Furthermore, a high-fat diet preserved MCAD and citrate synthase activities during pressure overload, suggesting that it may help maintain mitochondrial oxidative capacity in failing myocardium.

Topics: Acyl-CoA Dehydrogenase; Adiposity; Animals; Biomarkers; Blood Glucose; C-Reactive Protein; Citrate (si)-Synthase; Dietary Fats; Disease Models, Animal; Disease Progression; Fatty Acids, Nonesterified; Heart Failure; Hypertension; Hypertrophy, Left Ventricular; Inflammation Mediators; Insulin; Interleukin-6; Leptin; Male; Mice; Mice, Inbred C57BL; Mitochondria, Heart; Mitochondria, Muscle; Muscle, Skeletal; Myocardial Contraction; Myocardium; Oxidation-Reduction; RNA, Messenger; Time Factors; Triglycerides; Tumor Necrosis Factor-alpha; Ventricular Remodeling

A genetic study was carried out among obese and hypertensive individuals from India to assess allelic association, if any, at three candidate loci: Apolipoprotein B (ApoB) minisatellite and two tetranucleotide repeat loci; LPL (Lipoprotein lipase) and Leptin. Attempt has also been made to find out whether telomere length attrition is associated with hypertension and obese individuals.. Venous blood samples were collected from 37 normal, 35 obese and 47 hypertensive individuals. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMC) and PCR amplifications were achieved using locus specific primers. Genotyping of ApoB minisatellite was performed using 4% polyacrylamide gel electrophoresis (PAGE) followed by silver staining, whereas LPL and Leptin loci were genotyped using ALF Express DNA sequencer. Telomere length was determined using a recently developed real time based quantitative PCR, where the relative telomere length was determined by calculating the relative ratio of telomere (T) and single copy gene (S) PCR products which is expressed as T/S ratio.. All the three loci are highly polymorphic, display high heterozygosity and conform to Hardy-Weinberg's equilibrium expectations. ApoB minisatellite displayed 14 alleles, whereas LPL and Leptin tetranucleotide loci were having 9 and 17 alleles, respectively. Interestingly two new alleles (9 and 11 repeats) were detected at ApoB locus for the first time. The alleles at Leptin locus were classified as Class I (lower alleles: 149-200 bp) and Class II alleles (higher alleles: >217 bp). Higher alleles at ApoB (>39 repeats), predominant allele 9 at LPL and alleles 164 bp and 224 bp at Leptin loci have shown allelic association with hypertensive individuals. After adjusting the influence of age and gender, the analysis of co-variance (ANCOVA) revealed the relative telomere length (T/S ratio) in hypertensive individuals to be (1.01 +/- 0.021), which was significantly different (P < 0.001) from obese (1.20 +/- 0.023) and normal (1.22 +/- 0.014) individuals. However, no significant difference in the relative telomere length was observed among male and female individuals, although age related decrease in telomere length was observed in these limited sample size.. The present study revealed that allelic association at ApoB, LPL, Leptin loci and loss of telomere length may have strong genetic association with hypertensive individuals. However, further study on larger sample size is needed to draw firm conclusions.

Topics: Adolescent; Adult; Aged; Alleles; Apolipoproteins B; Child; Female; Gene Frequency; Genetic Markers; Genetic Predisposition to Disease; Humans; Hypertension; India; Leptin; Lipoproteins, LDL; Male; Middle Aged; Obesity; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Telomere; Young Adult

Data from animal studies clearly indicate an association between leptin and hypertension; results of human studies are less concordant. We investigated the role of leptin in obesity-related higher blood pressure (BP) in Japanese Americans living in Hawaii and Japanese in Japan. Serum leptin and BP were examined by standardized methods in men and women ages 40 to 59 years from 2 population samples, one Japanese American in Hawaii (88 men and 94 women) and the other Japanese in central Japan (123 men and 111 women). Multiple linear regression models were used to assess role of leptin in obesity-related higher BP. Across quartiles of leptin, there were significantly higher mean body mass index levels, systolic BP, and diastolic BP for both sexes and sites (P<0.01 to 0.02). In multivariate regression analyses using all of the data combined, relations of body mass index and leptin to systolic BP and diastolic BP remained significant with the interaction term (body mass index x log-leptin) in the models (P<0.01 to <0.05). These findings are consistent with the inference that leptin may be an independent mediator for obesity-related elevations in BP.

Topics: Adult; Asian; Asian People; Blood Pressure; Body Mass Index; Female; Hawaii; Humans; Hypertension; Japan; Leptin; Life Style; Linear Models; Male; Middle Aged; Multivariate Analysis; Obesity

Studies in adult population have suggested that leptin might play a role in inducing obesity related hypertension mediated by the sympathetic nervous system. This association has not been established for adolescents. Our study is designed to explore the relationship between leptin and norepinephrine levels in pediatric patients and to identify any contributors to hypertension for this population.. Thirty-nine obese adolescents, divided into four groups by gender and hypertension status were included in the study. Leptin and norepinephrine levels were measured during oral glucose tolerance tests (OGTT) to optimize hormonal secretion. T tests were used to compare baseline levels of glucose, insulin, leptin and norepinephrine at 0 hour point of OGTT between the hypertensive and normotensive patients for both genders. Analysis of covariance (ANCOVA) was used for comparison of subsequent levels between the hypertensive and normotensive groups for in both genders, with the corresponding baseline level as the covariance. Models with and without BMI adjustment were created and their results were found to be consistent. Correlation between leptin and norepinephrine was examined at each time point and through analysis of area under the curve (AUC).. Contrary to the previous findings obtained in adult patients, our results did not show any direct relationships between levels of leptin and norepinephrine. A slight decrease in norepinephrine level at 1 hour in the normotensive male group and a significant increase in leptin level at 1 hour in the hypertensive female group was observed.. Our preliminary data suggest that norepinephrine and leptin levels at 0 and 1 hour during routine OGTT, for males and females, respectively, may help identify a subgroup of obese adolescents who have higher risk for hypertension and cardiovascular complications.

Topics: Adolescent; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Leptin; Male; Norepinephrine; Obesity; Risk Factors; Sympathetic Nervous System

To determine the presence of traditional and emergent cardiovascular risk factors and to evaluate the triglyceride/high-density lipoprotein cholesterol (Tg/HDL-C) ratio as a marker for cardiovascular disease and metabolic syndrome (MS) in obese children.. Sixty-seven prepubertal children of both sexes, between the ages of 6 and 12 yr, 20 normal-weight children, 18 overweight, and 29 obese subjects, were studied. Anthropometric measures, blood pressure, body mass index (BMI), and fat mass (FM), were measured. Plasma glucose, serum insulin, lipid profile, C-reactive protein (CRP), and leptin concentrations were quantified. Glucose and insulin concentrations 2 h post-glucose load were determined. The Tg/HDL-C ratio, homeostasis model assessment index (HOMA), and quantitative insulin sensitivity check index (QUICKI) were calculated.. Systolic, diastolic, and mean blood pressures (MBP), low-density lipoprotein cholesterol (LDL-C), Tg/HDL-C, total cholesterol/HDL-C, LDL-C/HDL-C ratios, basal and 2 h postload insulin, CRP, and leptin were significantly higher and the QUICKI index were lower in the obese group. MBP, Tg/HDL-C ratio, HOMA, CRP, and leptin levels showed a positive and significant correlation and QUICKI a negative correlation with abdominal circumference, BMI, and FM. The Tg/HDL-C ratio correlated positively with MBP. The frequency of MS in the obese group was 69%. While Tg/HDL-C ratio, CRP, and leptin were higher and the values of QUICKI were lower in subjects with MS, it was the Tg/HDL-C ratio and the BMI that significantly explained the MS.. Obesity increases the cardiovascular risk in childhood. The Tg/HDL-C ratio could be a useful index in identifying children at risk for dyslipidemia, hypertension, and MS.

Topics: Blood Pressure; C-Reactive Protein; Cardiovascular Diseases; Child; Cholesterol, HDL; Female; Homeostasis; Humans; Hypertension; Insulin Resistance; Leptin; Male; Metabolic Syndrome; Obesity; Risk Factors; Triglycerides

Topics: alpha-MSH; Animals; Disease Models, Animal; Down-Regulation; Genetic Predisposition to Disease; Hypertension; Leptin; Melanocortins; Protein Precursors; Rats; Rats, Inbred SHR; Rats, Wistar; Thyrotropin-Releasing Hormone

Leptin is a hormone which is predominantly secreted by adipose tissue. Recent studies have shown that leptin increases arterial blood pressure. Although data from available animal studies clearly indicate an association between leptin and hypertension, results of human studies have been less definitive. We conducted a case-control study to examine the association between serum leptin levels and hypertension in 111 hypertensive subjects and 222 male controls, using conditional logistic regression analyses. Mean serum leptin levels were found to be marginally higher in the case subjects than in the control subjects (3.3 ng/ml versus 3.0 ng/ml), however, conditional logistic regression analysis revealed that subjects in the highest quartile had a significantly increased risk of hypertension compared with those in the lowest quartile, even after adjusting for drinking status and diabetes mellitus (adjusted OR, 2.11;95% CI, 1.01-4.39). Our findings suggest that leptin plays an important role in the development of hypertension.

Topics: Biomarkers; Blood Pressure; Case-Control Studies; Humans; Hypertension; Japan; Leptin; Logistic Models; Male; Middle Aged; Predictive Value of Tests

Leptin is a polypeptide hormone (167 amino acids, molecular weight of about 16kDa), synthesized mainly in white adipose tissue. The hormone plays an important role in regulation of hunger and satiety processes, in metabolism of carbohydrates and fats, development of cardio-vascular diseases and obesity. The occurrence of the increased level of leptin in pregnant women with hypertension, especially in women with preeclampsia, has also been brought to our attention. In recent years it has been suggested that the presence of different variants of leptin and leptin receptor genes may modify the leptin level in serum, and, in this way, influence an increased risk of obstetric complications, such as preeclampsia or eclampsia.. We have analyzed a group of 103 hypertensive pregnant women--61 women with gestational hypertension (GH) and 42 women with preeclampsia (PE). The control group consisted of 113 healthy pregnant women who have been investigated. Gestational hypertension and preeclampsia were recognized with the help of and assessed according to the ACOG criteria. The (-2548G/A) polymorphism was determined using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP).. In our study, a higher frequency of mutated AA genotype in GH group and PE groups (21.31% and 21.43% respectively vs. 16.81% in the controls) and the overrepresentation of mutated A allele in both analyzed groups (47.54% and 45.24% respectively vs. 41.59% in the controls) have been observed, without statistically significant differences.. The overrepresentation of AA genotypes and higher frequency of mutated A allele of (-2548G/A) polymorphism of leptin gene in GH and PE groups might indicate its possible contribution in gestational hypertension and preeclampsia.

Topics: Adult; Case-Control Studies; DNA Mutational Analysis; Female; Genotype; Humans; Hypertension; Leptin; Point Mutation; Polymerase Chain Reaction; Polymorphism, Genetic; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular

The role of adiponectin, a marker of the metabolic syndrome, on the pathogenesis of hypertension in comparison with markers of adipose tissue mass (leptin) and inflammation (high-sensitivity C-reactive protein [hs-CRP]) remains to be clarified. The eligible study population consisted of 2,045 residents aged > or =40 years who had participated in a community-based survey and had complete data for serum adiponectin, leptin, and hs-CRP, and for whom homeostasis model assessment of insulin resistance (HOMA-IR) had been calculated from insulin and plasma glucose. Among all eligible participants, as well as in the subgroup of nondiabetic normotensives (blood pressure <140/90 mmHg and without antihypertensive medication), all three markers were significantly correlated with systolic blood pressure (negative correlation for adiponectin and positive correlations for leptin and hs-CRP). Among all participants, systolic blood pressure and the presence of hypertension were determined mainly by age, sex, body mass index, and waist circumference. None of the markers further contributed to the multivariate linear regression or logistic regression models. In contrast, adiponectin, but not leptin, hs-CRP, or HOMA-IR, was significantly associated with systolic blood pressure and the presence of pre-hypertension (blood pressure within 120-139/80-89 mmHg) after adjustment for age, sex, body mass index, and waist circumference in the nondiabetic normotensive subgroup. Similarly, adiponectin was independently associated with diastolic blood pressure in the nondiabetic normotensive subgroup but not in the whole population. In conclusion, adiponectin, but not leptin or hs-CRP, was independently associated with blood pressure in a nondiabetic normotensive subgroup.

Topics: Abdominal Fat; Adiponectin; Adult; Aged; Biomarkers; Blood Pressure; C-Reactive Protein; Cross-Sectional Studies; Female; Health Surveys; Humans; Hypertension; Inflammation; Leptin; Linear Models; Logistic Models; Male; Metabolic Syndrome; Middle Aged; Obesity

We previously reported a significant association between plasma leptin (LPT) concentration and blood pressure (BP), which was partly independent of serum insulin levels and insulin resistance. The aims of this study were to detect whether serum LPT levels predict the development of hypertension (HPT) in the 8-yr follow-up investigation of a sample of an adult male population (the Olivetti Heart Study), and to evaluate the role of body mass index (BMI) and insulin resistance in this putative association.. The study population was made up of 489 untreated normotensive subjects examined in 1994-1995 (age: 50.1 +/- 6.7 yr; BMI: 26.3 +/- 2.8 kg/m(2); BP: 120 +/- 10/78 +/- 6 mm Hg; and homeostatic model assessment index: 2.1 +/- 1.6).. The HPT incidence over 8 yr was 35%. The participants with incident HPT had similar age but higher BMI (P < 0.001), serum LPT (P < 0.001), and BP (P < 0.01) at baseline. One sd positive difference in baseline serum LPT log was associated at univariate analysis with a 49% higher rate of HPT [95% confidence interval (CI) 22-83; P < 0.001]). In three different models of multivariable logistical regression analysis, LPT was respectively associated with a 41% greater risk to develop HPT (95% CI 15-74; P < 0.001) upon adjustment for age and baseline BP, with a 48% (95% CI 20-81) greater risk when adding the homeostatic assessment model index to the model, and with 33% greater risk (95% CI 6-67; P < 0.02) upon adjustment for BMI.. In this sample of originally normotensive men, circulating LPT level was a significant predictor of the risk to develop HPT over 8 yr, independently of BMI and insulin resistance.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Body Weight; Case-Control Studies; Follow-Up Studies; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Risk Factors

Previously, we have demonstrated that leptin increases blood pressure (BP) in the rats through two oxidative stress-dependent mechanisms: stimulation of extracellular signal-regulated kinases (ERK) by H(2)O(2) and scavenging of nitric oxide (NO) by superoxide (O(2-.)). Herein, we examined if renal glutathione system and antioxidant enzymes determine the mechanism of prohypertensive effect of leptin. Leptin administered at 0.5 mg/kg/day for 4 or 8 days increased BP and renal Na(+),K(+)-ATPase activity and reduced fractional sodium excretion; these effects were prevented by NADPH oxidase inhibitor, apocynin. Superoxide scavenger, tempol, abolished the effect of leptin on BP and renal Na(+) pump in rats receiving leptin for 8 days, whereas ERK inhibitor, PD98059, was effective in animals treated with leptin for 4 days. Leptin administered for 4 days decreased glutathione (GSH) and increased glutathione disulfide (GSSG) in the kidney. In animals receiving leptin for 8 days GSH returned to normal level, which was accompanied by up-regulation of gamma-glutamylcysteine synthetase (gamma-GCS), a rate-limiting enzyme of the GSH biosynthetic pathway. In addition, superoxide dismutase (SOD) activity was decreased, whereas glutathione peroxidase (GPx) was increased in rats receiving leptin for 8 days. Cotreatment with gamma-GCS inhibitor, buthionine sulfoximine (BSO), accelerated, whereas GSH precursor, N-acetylcysteine (NAC), attenuated leptin-induced changes in gamma-GCS, SOD, and GPx. In addition, coadministration of BSO changed the mechanism of BP elevation from H(2)O(2)-ERK to (O(2-.))-NO dependent in animals receiving leptin for 4 days, whereas NAC had the opposite effect in rats treated with leptin for 8 days. These results suggest that initial change in GSH redox status induces decrease in SOD/GPx ratio, which results in greater amount of (O)2-.)) versus H(2)O(2) in later phase of leptin treatment, thus shifting the mechanism of BP elevation from H(2)O(2)-ERK to (O(2-.))-NO dependent.

Topics: Animals; Antioxidants; Enzyme Inhibitors; Hydrogen Peroxide; Hypertension; Kidney; Leptin; Male; Oxidation-Reduction; Rats; Rats, Wistar; Sodium; Superoxides; Time Factors

This study investigated the effects of rosiglitazone on nutritionally programmed chronic disease, with a focus on blood pressure (BP) and aortic wall structural remodeling. Wistar pregnant rats were fed one of two diets: a normal protein diet (19% protein; NP rats) or low-protein diet (5% protein; LP rats). Male offspring at 3 months of age were randomly divided into four groups: NP offspring treated with rosiglitazone (NPR); untreated NP offspring (NP); LP offspring treated with rosiglitazone (LPR); untreated LP offspring (LP). Rosiglitazone was administered at a dose of 5 mg/kg/d until 6 months of age. BP was elevated in LP offspring. Rosiglitazone reduced BP beginning in the first week of treatment in the LPR offspring. The insulin sensitivity was increased in LP offspring, and was not altered by rosiglitazone. LP offspring exhibited a 40% reduction in the amount of elastic fibers in the aorta wall compared with NP offspring (p < 0.01), and the quantity of elastic fibers was not altered by rosiglitazone. The smooth muscle cells, elastic lamellae, circumferential wall tension (CWT) and tensile stress (TS) were increased in LP offspring, indicating increased blood flow in the aorta. Rosiglitazone reduced both CWT and TS by 30% compared to the levels in untreated LP offspring (p < 0.01 for both). Rosiglitazone restored the expressions of angiotensin II type 1 receptor and endothelial nitric oxide synthase nearly to the levels in the NP offspring. ANOVA disclosed a significant two-factor interaction between protein content in the diet and rosiglitazone treatment (p < 0.001 for CWT and p < 0.00001 for TS, two-way ANOVA). We conclude that rosiglitazone has beneficial effects in reducing the BP and the aortic tunica media hypertrophy with consequent balance of the wall stress in metabolically programmed offspring.

Topics: Animals; Aorta; Blood Glucose; Blood Pressure; Carbohydrate Metabolism; Diet, Protein-Restricted; Disease Models, Animal; Elasticity; Female; Hypertension; Hypertrophy; Insulin; Leptin; Male; Nitric Oxide Synthase Type III; PPAR gamma; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Rosiglitazone; Thiazolidinediones; Tunica Media

Adipocytes regulate blood vessel formation, and in turn endothelial cells promote preadipocyte differentiation through the expression of proangiogenic factors, such as vascular endothelial growth factor (VEGF)-A. Some adipocytokines and hormones also have an effect on vascular development.. Our objectives were to analyze the relationship between weight and circulating VEGF-A in morbidly obese subjects before and after bariatric surgery, and investigate the relationship between circulating VEGF-A and certain adipocytokines and hormones regulating adipocytes.. A total of 45 morbidly obese women and nine lean females were included in the study. Patients underwent bariatric surgery: vertical banded gastroplasty (n=17), gastric bypass (n=17), and biliopancreatic diversion (n=11). Serum samples for VEGF-A, adiponectin, leptin, ghrelin, and insulin were obtained preoperatively and 9-12 months after surgery.. Obese patients showed significantly higher VEGF-A levels than controls (306.3+/-170.3 vs. 187.6+/-91.9 pg/ml; P=0.04), decreasing to 246.1+/-160.4 after surgery (P<0.001), with no differences among surgical procedures. In controls there was an inverse correlation between VEGF-A and ghrelin (r=-0.85; P<.01), but not in obese patients. Leptin and insulin concentrations were increased in obese patients, with a significant decrease shown after weight loss with surgery. Conversely, adiponectin concentrations were lower in obese patients, with a significant increase shown after weight loss with surgery. Ghrelin was higher in controls than obese patients, decreasing after gastric bypass and biliopancreatic diversion, but not after vertical banded gastroplasty.. Serum VEGF-A levels are significantly higher in obese patients than in lean controls, decreasing after weight loss with bariatric surgery, behaving similarly to other hormones related to adipose mass like leptin and insulin.

Topics: Adipokines; Adult; Aged; Bariatric Surgery; Diabetes Mellitus, Type 2; Female; Ghrelin; Humans; Hypertension; Insulin; Leptin; Middle Aged; Obesity, Morbid; Sleep Apnea, Obstructive; Vascular Endothelial Growth Factor A; Weight Loss; Young Adult

Hearts of NaCl-induced hypertensive-glucose intolerant (HGI) rats develop reduced infarcts after ischemia-reperfusion injury (IRI) than their hypertensive (H) counterparts. Because high intake of saturated fat is a major risk factor for ischemic heart disease, we tested the hypothesis that chronic (18 weeks) consumption of a high saturated fat diet increases susceptibility to IRI, an effect more marked in the HGI rats than in the H rats. The fat-fed H (HFAT) rat displayed significantly higher body weight and plasma leptin content compared to the H, HGI, or fat-fed HGI (HGIFAT) rats which all showed similar values. In contrast, plasma triglyceride concentration was significantly higher in the HGIFAT rat than in the other three groups. Plasma insulin concentration was similar in the two H groups but higher than that of the two HGI groups. Compared to the H rat, the HGI rat was markedly glucose intolerant, with fat feeding causing comparable worsening of glucose intolerance in each group. The HGIFAT rats displayed a reduction in baseline myocardial contractility and relaxation and a higher end-diastolic pressure compared to the other three groups. Infarct size was significantly lower in the HGI rats than in the H rats. Although fat feeding did not affect infarct size of the H rat, it worsened that of the HGIFAT rat thereby abrogating the differential that existed between the H and HGI rats. In conclusion, excess fat feeding impairs myocardial function of HGI rats and increases their susceptibility to IRI. These findings are of relevance to the metabolic syndrome that manifests as a cluster of insulin resistance, dyslipidemia, and systemic hypertension.

Topics: Animals; Blood Glucose; Blood Pressure; Body Weight; Dietary Fats; Disease Models, Animal; Glucose Intolerance; Hypertension; Insulin; Leptin; Male; Metabolic Syndrome; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion Injury; Rats; Rats, Inbred WKY; Sodium Chloride, Dietary; Streptozocin; Time Factors; Triglycerides; Ventricular Pressure

In animals, the adipocyte-derived hormone leptin induces increased blood pressure centrally via the hypothalamus, and one study has reported that exercise training decreases hypothalamic leptin receptor expression. In humans, high circulating leptin concentrations are associated with high blood pressure, but the possible influence of physical activity or aerobic capacity on this association is unknown.. Forty-two healthy women, 25-40 years of age, with diverse ranges of body fatness and aerobic capacities, were studied under basal resting conditions. Blood pressure (sphygmomanometry), arterial stiffness (pulse wave velocity (PWV)), percent body fat (dual energy X-ray absorptiometry), circulating concentrations of leptin, soluble leptin receptor (sLR) (enzyme-linked immunoassay), and nitric oxide (Griess reaction) were measured.. Serum leptin correlated with percent body fat (R(2) = 0.74, P < 0.0001) but was not significantly associated with aerobic capacity. Blood pressure correlated positively with serum leptin concentrations and had a negative interaction with aerobic capacity for both systolic (overall model: R(2) = 0.33, P = 0.002) and diastolic (R(2) = 0.48, P < 0.0001) pressure. The relation between leptin and blood pressure was attributable solely to women with below-median aerobic capacity even though their body fat percentages and leptin concentrations were similar to those of women above the median. The results could not be attributed to differences in peripheral factors such as sLR or nitric oxide concentrations or to differences in arterial stiffness determined by aortic PWV.. Circulating leptin concentrations are related to body fatness, but the hypertensive influence of leptin is modified by physical fitness.

Topics: Adult; Blood Flow Velocity; Blood Pressure; Body Composition; Exercise; Female; Humans; Hypertension; Leptin; Nitric Oxide; Obesity; Regression Analysis

A significant association between hypertension and obesity has been noted in several epidemiological studies. In particular, a progressive increase has been demonstrated, both in men and women, in the prevalence of hypertension in relation to the different measures of obesity. Such association is independent of age, gender, and also probably the ethnic group. It has also been shown that obesity may antedate and predict the development of hypertension. Even among subjects with normal or optimal blood pressure, the obese subjects are more likely to develop high blood pressure levels in the following years. The opposite can also be true. Hypertensive subjects are more likely to develop obesity than normotensive ones. It has been suggested that initial sympathetic hyperactivity may lead to high blood pressure and progressive hyperstimulation, followed by down-regulation, of beta-adrenergic receptors, with subsequent development of obesity because of the lesser beta-adrenoceptor that induces dissipation of calories. Visceral obesity seems to be more important than subcutaneous obesity with respect to high blood pressure. Finally, in addition to the well established relation between low weight at birth and adult hypertension, it has also been shown that any transient increases in body weight may be paralleled by increases in blood pressure at any time in life. Obesity may be associated with hypertension through an increased sympathetic tone, increased fluid retention and insulin resistance. Animal models of hypertension associated with obesity may be suitable to investigate in detail the pathophysiological mechanisms of such association. In this setting decreased nitric oxide production and resistance to leptin have been identified as important determinants of obesity in hypertension. From a therapeutic standpoint, it is well known that weight reduction is associated with a drop in blood pressure. Unfortunately, however, obese hypertensive subjects who loose weight in the short term often do not succeed to maintain the weight loss, with consequent new gain in body weight and blood pressure. Thus, weight reduction should be maintained in the long term to elicit a sustained and effective antihypertensive efficacy.

Topics: Adult; Animals; Body Mass Index; Clinical Trials as Topic; Disease Models, Animal; Female; Follow-Up Studies; Humans; Hypertension; Leptin; Male; Meta-Analysis as Topic; Nitric Oxide; Obesity; Practice Guidelines as Topic; Prevalence; Risk Factors; Sex Factors; Time Factors; Weight Gain; Weight Loss

The present study was carried to develop and analyze the consequences of hypercaloric pellet-diet cycle that promotes obesity in rats. Male Wistar rats were randomly distributed into two groups that received either normal diet (ND; n =32; 3,5 Kcal/g) or a hypercaloric diet (HD; n =32; 4,6 Kcal/g). The ND group received commercial Labina rat feeding while the HD animals received a cycle of five hypercaloric diets over a 14-week period. The effects of the diets were analyzed in terms of body weight, body composition, hormone-metabolite levels, systolic arterial pressure and glucose tolerance at the 5% significance level. The hypercaloric pellet diet cycle promoted an increase in body weight and fat, systolic arterial pressure and a high serum level of glucose, triacylglycerol, insulin and leptin. The HD group also presented an impaired glucose tolerance. In conclusion, the results of this study show that the hypercaloric pellet-diet cycle promoted obesity in Wistar rats and displayed several characteristics that are commonly associated with human obesity, such as high arterial pressure, insulin resistance, hyperglycaemia, hyperinsulinaemia, hyperleptinaemia and dyslipidaemia.

Topics: Analysis of Variance; Animals; Blood Pressure; Body Composition; Body Weight; Dietary Fats; Disease Models, Animal; Dyslipidemias; Energy Intake; Humans; Hyperglycemia; Hyperinsulinism; Hypertension; Leptin; Male; Obesity; Random Allocation; Rats; Rats, Wistar

Previous studies showed relation between elevated serum leptin levels (SLL) and hypertension. The aim of this study was to evaluate relationship between SLL and left ventricular hypertrophy (LVH) and body mass index (BMI) in obese hypertensive patients.. Eighty patients with newly diagnosed essential hypertension were included in this cross-sectional, case-controlled study. Hypertensive patients were classified as; level-I or level-II according to JNC-VII classification and as normal weighted (18-24.99 kg/m2), over weighted (25-26.99 kg/m2) and obese (27 kg/m2 and above) according to BMI's. All the patients were evaluated by echocardiography and blood samples were withdrawn for determination SLL. Statistical analysis was performed using Wilcoxon sign rank, Mann Whitney U and Kruskal Wallis tests. Logistic regression analysis was applied for the evaluation of relationship between SLL and clinical variables.. Mean levels of arterial blood pressure (ABP) of total 80 patients (36 males and 44 females) was 155+/-1.1/95.1+/-0.7 mmHg and the mean age was 48.9+/-1.3 years. Patients with level I hypertension (n=32) had mean ABP of 149.7+/-0.5/90.9+/-0.6 mmHg and with level-II hypertension (n=48)--mean ABP 168.5+/-1.6/102.9+/-0.9 mmHg. The mean BMI in normal weighted group (n=26) was 22.7+/-0.3 kg/m2, over weighted group (n=19)-26.1+/-0.2 kg/m2 and obese group (n=35)-30.9+/-0.5 kg/m2. There were no differences in LVH incidence between hypertension level groups and BMI groups (p>0.05). Serum leptin levels were similar in patients with level I and level II hypertension (33.5+/-2.9 ng/ml and 37.3+/-3.6 ng/ml, respectively, p>0.05). However, leptin levels were higher in obese patients as compared with normal and over weighted patients (40.9+/-3.2 ng/ml versus 28.5+/-3.6 ng/ml and 32.8+/-4.9 ng/ml, p<0.01). Patients with LVH had significantly higher levels of leptin as compared with patients without LVH (51.40+/-5.1 ng/ml versus 28.30+/-4.20 ng/ml, p<0.05). Logistic regression analysis demonstrated that SLL independently of blood pressure and BMI is related with LVH (OR--1.7, %95 CI--1.2-1.9, p<0.05).. Our study showed that elevated serum leptin levels are significantly related with LVH independently of body mass index and level of blood pressure. Thus, elevated SLLs, independently of hypertension level and BMI classification, coexist with LVH. Sympathetic activation or direct cardiac receptor activation or proliferative effects of leptin may be responsible for this coexistence.

Topics: Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Logistic Models; Male; Middle Aged; Obesity; Risk Factors

Topics: Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Logistic Models; Male; Middle Aged; Obesity; Risk Factors

To examine the association of a common -2548G/A (rs7799039) promoter variant of the human leptin gene (LEP) with obesity or body mass index (BMI) and its associated phenotypes such as blood pressure variability and the prevalence of hypertension in a sample of the Tunisian population.. Two hundred and twenty-nine obese patients were screened and compared with 251 normal weight subjects. The -2548G/A LEP polymorphism was analysed by PCR-RFLP procedure.. No significant association was found between the -2548G/A polymorphism and obesity or BMI. However, in obese patients subjects with AA genotype had significantly higher systolic (p = 0.003) and diastolic (p = 0.002) blood pressure compared with those with GA or GG genotypes. Stratified analysis by gender revealed that male patients but not female homozygous for -2548A allele exhibited significantly increased systolic (p = 0.01) and diastolic (p<0.001) blood pressure than did carriers of -2548G allele. Multiple linear regression analysis revealed that AA genotype significantly affect systolic and diastolic blood pressure in obese men. Additionally, significant association between AA genotype and higher prevalence of hypertension was found in male patients (p = 0.03).. The present study showed that the -2548G/A LEP polymorphism is associated with blood pressure in obese male patients.

Topics: Adult; Blood Pressure; Case-Control Studies; Female; Genotype; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Polymorphism, Genetic; Promoter Regions, Genetic; Sex Factors; Tunisia

Topics: Blood Pressure; Central Nervous System; Humans; Hypertension; Hypothalamus; Interleukin-6; Leptin; Obesity; Peripheral Nervous System; Sympathetic Nervous System; Tumor Necrosis Factor-alpha

Obstructive sleep apnea syndrome (OSAS) is frequently complicated by metabolic syndrome, including diabetes and hypertension. Both OSAS and metabolic syndrome are strongly associated with obesity. Recently, adiponectin and leptin, which are secreted by adipose tissue, have been considered to play important roles in the progression of these diseases. Thus, to examine the association between leptin, adiponectin and OSAS, we measured the serum level of these adipocytokines in the same OSAS patients.. Sixty-eight consecutive Japanese men, who recorded all-night polysomnography, were enrolled in this study, and were divided into three groups, control (n=15), moderate OSAS (n=21) and severe OSAS (n=32). We measured serum levels of adiponectin and leptin by ELISA.. Serum leptin levels were positively correlated with apnea hypopnea index (AHI) (r=0.552, p<0.001), the percentage of time with less than 90% hemoglobin saturation level in total sleep time (%T<90) (r=0.399, p<0.001) and body mass index (BMI) (r=0.807, p<0.0001). These parameters were suggested as the determinant factor for the serum leptin level by stepwise multiple regression analysis. On the other hand, serum adiponectin levels showed a positive correlation with age (r=0.361, p=0.005) and HDL-cholesterol level (r=0.274, p=0.039). Although there was no significant correlation between serum adiponectin levels and AHI or %T<90, serum adiponectin levels were chosen at a determinant factor of %T<90.. These results suggested that the increasing severity of OSAS induces an increase in setum leptin concentration, but the serum adiponectin levels may be regulated independently of the degree of OSAS, obesity and serum leptin levels in patients with OSAS.

Topics: Adipokines; Adiponectin; Adult; Body Mass Index; Cholesterol, HDL; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Polysomnography; Sleep Apnea, Obstructive

Obesity is directly and strongly associated with hypertension and left ventricular hypertrophy (LVH). Development of LVH is multifactorial, caused both by haemodynamic and non-haemodynamic factors. Hypertension is the main haemodynamic factor. Humoral mechanisms, as a non-haemodynamic factor for LVH development, have not been completely explained. The aim of this study is to determine whether hyperleptinemia can be one of humoral--non-haemodynamic factor inducing LVH together with haemodynamic factors in overweight females. The study was done on thirty six adult, overweight female patients, body mass index in range 25-30 kg/m2. Patients are nondiabetic with regular renal function. Twenty one female patients were hypertensive with left ventricular hypertrophy. Control group included fifteen hypertensive female patients without left ventricular hypertrophy. In all patients was determined glucose profile and creatinine clearance, cholesterol, triglycerides, LDL, HDL. Weight, high, circumference of the waist and hips was taken. Cardiovascular determination was done applying two-dimensional ultrasound. Serum leptin level was measured using radioimmunoassay method (RIA). Results showed that serum leptin level was significantly higher in hypertensive, overweight females with LVH. This suggests that non-haemodynamic factors, such as hyperleptinemia, participate in left ventricular hypertrophy development together with haemodynamic factors in adult hypertonic, overweight females.

Topics: Aged; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Middle Aged; Overweight; Risk Factors

To evaluate the role of leptin, a 16-kDa adipocyte-derived hormone, in the development of metabolic dysregulation of psoriasis.. Case-control study.. Referral centers. Patients Seventy-seven patients with psoriasis and 81 age- and sex-matched control subjects were included in the study. Intervention Enzyme-linked immunoassay of serum samples from study subjects.. Serum leptin levels and proportions of comorbidities (including hypertension, diabetes mellitus, metabolic syndrome, hypertriglyceridemia, and reduced high-density lipoprotein cholesterol concentrations) in cases vs controls were compared using chi(2) and Mann-Whitney tests. The clinical significance of leptin in psoriasis was analyzed using logistic regression models.. Significantly more obesity (odds ratio [OR], 2.67) and hypertension (2.17) (P =.04 for both) were observed in subjects with psoriasis. High serum leptin levels (>or=7397.43 pg/mL) were found in female subjects (OR, 6.05; P < .001) and in subjects with obesity (3.45; P =.01), hypertension (2.19; P =.04), metabolic syndrome (3.58; P =.008), and psoriasis (2.25; P =.02). On multivariate analysis, psoriasis (OR, 4.57; P =.009) was significantly associated with hyperleptinemia independent of female sex (26.36; P < .001), metabolic syndrome (4.37; P =.04), and obesity (2.83; P =.12). Finally, patients with psoriasis who had hyperleptinemia tended to be female (P < .001) and manifested obesity (P =.002) and metabolic syndrome (P =.003).. Hyperleptinemia is associated with psoriasis independent of female sex and other conventional cardiovascular risk factors such as obesity and metabolic syndrome. Hyperleptinemia in psoriasis may contribute to metabolic syndrome.

Topics: Adult; Aged; Case-Control Studies; Female; Humans; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Psoriasis; Risk Factors; Sex Factors

Obesity is an effect of interaction of genetic and environmental factors. It leads to development of serious complications, like insulin resistance, diabetes type 2, arterial hypertension and atherosclerosis. The adipose tissue is a place where many adipokines, mainly leptin and adiponectin, are produced and released. Adiponectin, which blood level is decreased in obesity is considered to have antidiabetic and antiatherogenic effect. While leptin, which blood level is increased in obesity, is associated with regulation of appetite, energy expenditure, lipids and carbohydrates metabolism, cellular differentiation and puberty. The aim of this research was estimation of leptin to adiponectin ratio (Lep/AdipoR) in the blood of patients who came from obese families. The study was carried out on 80 patients (43 female and 37 male). The antropometric examination with proportional contents of adipose tissue, oral glucose tolerance test (OGTT) and oral postprandial lipaemia test (OPLT) were performed. The fasting level of leptin (Elisa), adiponectin (Elisa) and von Willebrand factor (Elisa) lipidogram were performed. During OGTT blood was sampled in intervals of 30 minutes up to 2 hours, to measure glucose and insulin concentration. In fasting state and then every 2 hours after consumption of a high-fat meal (OPLT), (0, 2 hours, 4 hours, 6 hours, and 8 hours) blood was sampled for: trigliceride, glucose, free fatty acids and insulin concentration. The insulin resistance ratio (HOMA-IR) was calculated for each patient according to the formula: [insulin (mU/ml) x glucose (mmol/l)]/22.5. Adiponectin blood level was higher in the examined women than in men. It (regardless to the sex) was decreased with decrease of body mass index (BMI). Blood level of leptin (also higher in women) was positively corelated with BMI. In the group of patients with low level of adiponectin in serum (below 5mg/ml in men and 10 mg/ml in women) the highest con- centration of glucose and insulin in successive time points of OGTT and the highest HOMA-IR value (4.79 in men and 4.38 in women) were observed. In patients with high level of leptin in serum (over 20 ng/ml), the highest concentration of insulin, especially in 2 hours of the test (101.75 micromol/ l), and the highest HOMA-IR value (4.30 during OPLT ) were found. The Lep/AdipoR in the blood was significantly higher in obese patients in comparison to people with normal BMI. Lep/AdipoR had high correlation factor with BMI (r = 0.6267, p

Topics: Adiponectin; Adipose Tissue; Atherosclerosis; Female; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; ROC Curve

To examine the relation of well-known factors of the metabolic syndrome (MetS) as well as related circulating factors, with risk of colorectal cancer.. We performed a case control study of 306 colorectal cancer cases and 595 matched controls nested in the Northern Sweden Health and Disease Cohort. Levels of C-peptide, glycated haemoglobin (HbA1c), leptin and adiponectin were measured in cryopreserved samples. Body mass index (BMI), systolic and diastolic blood pressure and fasting and post-load plasma glucose, had been measured in a subcohort. Conditional logistic regression was used to calculate odds ratios (OR) of disease, including risk assessments for the MetS factors: obesity (BMI>30 kg m(-2)), hypertension (blood pressure > or =140/90 mmHg or use of anti-hypertensive drugs) and hyperglycaemia (fasting glucose > or =6.1 mmol l(-1) or post-load glucose in capillary plasma > or =8.9 mmol l(-1)).. None of the studied variables were significantly associated with risk across quartiles. Presence of obesity, hypertension and hyperglycaemia significantly increased the risk of colorectal cancer; OR for three vs null factors was 2.57 (95% Confidence Interval [CI] 1.20-5.52; P (trend)=0.0021), as compared to a 30 to 70% increased risk for the factors in single. Similarly, top decile levels of C-peptide, HbA1c and leptin/adiponectin ratio were associated with an increased risk; ORs for top vs deciles 1-9 were 1.56 (95% CI 0.93-2.62; P=0.090), 1.83 (95% CI 1.00-3.36; P=0.051) and 1.50 (95% CI 0.83-2.71; P=0.18), respectively.. Our study support the view that components of the MetS increase risk of colorectal cancer, and further suggests that only very high levels of metabolic factors confer an increased risk.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Blood Glucose; C-Peptide; Colorectal Neoplasms; Epidemiologic Methods; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypertension; Leptin; Male; Metabolic Syndrome; Middle Aged; Obesity; Sweden

The metabolic syndrome is a group of disorders including obesity, insulin resistance, atherogenic dyslipidemia, hyperglycemia, and hypertension. To date, few animal models have been described to recapitulate the phenotypes of the syndrome. In this study, we generated and characterized two lines of triple-knockout mice that are deficient in either apolipoprotein E (Apoe(-/-)) or low-density lipoprotein receptor (Ldlr(-/-)) and express no leptin (Lep(ob/ob)) or apolipoprotein B-48 but exclusively apolipoprotein B-100 (Apob(100/100)). These two lines are referred to as Apoe triple-knockout-Apoe 3KO (Apoe(-/-)Apob(100/100)Lep(ob/ob)) and Ldlr triple-knockout-Ldlr 3KO (Ldlr(-/-)Apob(100/100)Lep(ob/ob)) mice. Both lines develop obesity, hyperinsulinemia, hyperlipidemia, hypertension, and atherosclerosis. However, only Apoe 3KO mice are hyperglycemic and glucose intolerant and are more obese than Ldlr 3KO mice. To evaluate the utility of these lines as pharmacological models, we treated both with leptin and found that leptin therapy ameliorated most metabolic derangements. Leptin was more effective in improving glucose tolerance in Ldlr 3KO than Apoe 3KO animals. The reduction of plasma cholesterol by leptin in Ldlr 3KO mice can be accounted for by its suppressive effect on food intake. However, in Apoe 3KO mice, leptin further reduced plasma cholesterol independently of its effect on food intake, and this improvement correlated with a smaller plaque lesion area. These effects suggest a direct role of leptin in modulating VLDL levels and, likewise, the lesion areas in VLDL-enriched animals. These two lines of mice represent new models with features of the metabolic syndrome and will be useful in testing therapies targeted for combating the human condition.

Topics: Animals; Apolipoprotein B-48; Apolipoproteins E; Disease Models, Animal; Hyperglycemia; Hyperlipidemias; Hypertension; Insulin Resistance; Leptin; Lipoproteins, VLDL; Male; Metabolic Syndrome; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Phenotype; Receptors, LDL

We investigated if extracellular signal-regulated kinases (ERK) and oxidative stress are involved in the pathogenesis of arterial hypertension induced by chronic leptin administration in the rat. Leptin was administered at a dose of 0.25 mg/kg twice daily s.c. for 4 or 8 days. Blood pressure (BP) was higher in leptin-treated than in control animals from the third day of the experiment. The superoxide dismutase (SOD) mimetic, tempol, normalized BP in leptin-treated rats on days 6, 7 and 8, whereas the ERK inhibitor, PD98059, exerted a hypotensive effect on days 3 through 6. Leptin increased ERK phosphorylation level in renal and aortic tissues more markedly after 4 than after 8 days of treatment. In addition, leptin reduced urinary Na(+) excretion and increased renal Na(+),K(+)-ATPase activity, and these effects were abolished on days 4 and 8 by PD98059 and tempol, respectively. The levels of NO metabolites and cGMP were reduced in animals receiving leptin for 8 days. Markers of oxidative stress (H(2)O(2) and lipid peroxidation products) were elevated to a greater extent after 4 than after 8 days of leptin treatment. In contrast, nitrotyrosine, a marker of protein nitration by peroxynitrite, was higher in animals receiving leptin for 8 days. NADPH oxidase inhibitor, apocynin, prevented leptin's effect on BP, ERK, Na(+),K(+)-ATPase/Na(+) excretion and NO formation at all time points. SOD activity was reduced, whereas glutathione peroxidase (GPx) activity was increased in the group treated with leptin for 8 days. These data indicate that: (1) ERK, activated by oxidative stress, is involved only in the early phase of leptin-induced BP elevation, (2) the later phase of leptin-induced hypertension is characterized by excessive NO inactivation by superoxide, (3) the time-dependent shift from ERK to O(2)(-)-NO dependent mechanism may be associated with reduced SOD/GPx ratio, which favors formation of O(2)(-) instead of H(2)O(2).

Topics: Animals; Aorta; Blood Pressure; Cyclic N-Oxides; Disease Models, Animal; Drug Administration Schedule; Drug Therapy, Combination; Enzyme Inhibitors; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Hypertension; Injections, Subcutaneous; Kidney; Leptin; Male; Nitric Oxide; Oxidative Stress; Phosphorylation; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase; Spin Labels

We examined the role of epidermal growth factor (EGF) receptor in the pathogenesis of leptin-induced hypertension in the rat. Leptin, administered in increasing doses (0.1-0.5 mg/kg/day) for 10 days, increased phosphorylation levels of non-receptor tyrosine kinase, c-Src, EGF receptor and extracellular signal-regulated kinases (ERK) in aorta and kidney, which was accompanied by the increase in plasma concentration and urinary excretion of isoprostanes and H2O2. Blood pressure and renal Na+,K+-ATPase activity were higher, whereas urinary sodium excretion was lower in animals receiving leptin. The effects of leptin on renal Na+,K+-ATPase, natriuresis and blood pressure were abolished by NADPH oxidase inhibitor, apocynin, Src kinase inhibitor, PP2, EGF receptor inhibitor, AG1478, protein farnesyltransferase inhibitor, manumycin A, and ERK inhibitor, PD98059. In contrast, inhibitors of insulin-like growth factor-1 and platelet-derived growth factor receptors, AG1024 and AG1295, respectively, only slightly reduced ERK phosphorylation and had no effect on blood pressure in rats receiving leptin. These data indicate that: (1) experimental hyperleptinemia is associated with oxidative stress and c-Src-dependent transactivation of the EGF receptor, which stimulates ERK in vascular wall and the kidney, (2) overactivity of EGF receptor-ERK pathway contributes to leptin-induced hypertension by stimulating renal Na+,K+-ATPase and reducing sodium excretion, (3) inhibitors of c-Src, EGF receptor and ERK may be considered as a novel therapy for hypertension associated with hyperleptinemia, e.g. in patients with obesity and metabolic syndrome.

Topics: Animals; Aorta, Abdominal; Aorta, Thoracic; CSK Tyrosine-Protein Kinase; ErbB Receptors; Extracellular Signal-Regulated MAP Kinases; Glomerular Filtration Rate; Hypertension; Isoprostanes; Kidney; Leptin; Male; Oxidative Stress; Protein-Tyrosine Kinases; Rats; Rats, Wistar; Sodium; Sodium-Potassium-Exchanging ATPase; src-Family Kinases

Bardet-Biedl syndrome (BBS) is a heterogeneous genetic disorder characterized by many features, including obesity and cardiovascular disease. We previously developed knockout mouse models of 3 BBS genes: BBS2, BBS4, and BBS6. To dissect the mechanisms involved in the metabolic disorders associated with BBS, we assessed the development of obesity in these mouse models and found that BBS-null mice were hyperphagic, had low locomotor activity, and had elevated circulating levels of the hormone leptin. The effect of exogenous leptin on body weight and food intake was attenuated in BBS mice, which suggests that leptin resistance may contribute to hyperleptinemia. In other mouse models of obesity, leptin resistance may be selective rather than systemic; although mice became resistant to leptin's anorectic effects, the ability to increase renal sympathetic nerve activity (SNA) was preserved. Although all 3 of the BBS mouse models were similarly resistant to leptin, the sensitivity of renal SNA to leptin was maintained in Bbs4 -/- and Bbs6 -/- mice, but not in Bbs2 -/- mice. Consequently, Bbs4 -/- and Bbs6 -/- mice had higher baseline renal SNA and arterial pressure and a greater reduction in arterial pressure in response to ganglionic blockade. Furthermore, we found that BBS mice had a decreased hypothalamic expression of proopiomelanocortin, which suggests that BBS genes play an important role in maintaining leptin sensitivity in proopiomelanocortin neurons.

Topics: Animals; Bardet-Biedl Syndrome; Blood-Brain Barrier; Body Weight; Disease Models, Animal; Electrocardiography; Gene Expression Regulation; Group II Chaperonins; Hypertension; Leptin; Magnetic Resonance Imaging; Mice; Mice, Knockout; Microtubule-Associated Proteins; Molecular Chaperones; Obesity; Organ Size; Proteins

Microalbuminuria increases cardiovascular risk and is considered a metabolic disorder. Low glomerular filtration rate is also associated with increased cardiovascular risk, but the relation of low glomerular filtration rate to metabolic disorders is not well understood.. Designed as a cross-sectional, epidemiologic study, the Insulin Resistance Atherosclerosis Study was conducted in four centers: San Antonio (Texas), San Luis Valley (Colorado), and Oakland and Los Angeles (California). The Modification of Diet in Renal Disease equation was used to classify individuals without diabetes and with normoalbuminuria (n = 856; age 40 to 69 yr) by the presence or absence of low glomerular filtration rate (<60 ml/min per 1.73 m(2)). A direct marker of insulin resistance, the insulin sensitivity index, was measured by the frequently sampled intravenous glucose tolerance test.. Low glomerular filtration rate was related to hypertension and the metabolic syndrome. Low glomerular filtration rate was associated with fasting insulin concentration and insulin sensitivity index. Low glomerular filtration rate was also associated with insulin concentration after adjustment for potential determinants of glomerular filtration rate but was not associated with insulin sensitivity index.. Low glomerular filtration rate is associated with increased insulin concentration in individuals without diabetes and with normoalbuminuria. Longitudinal analyses are needed to determine whether insulin concentration (insulin resistance) precedes the deterioration of renal function.

Topics: Adult; Aged; Albuminuria; C-Reactive Protein; Cross-Sectional Studies; Diabetes Mellitus; Fasting; Glomerular Filtration Rate; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Metabolic Syndrome; Middle Aged; Southwestern United States

Topics: Animals; Humans; Hypertension; Leptin; Obesity

It is not known how carbohydrate and fat intake affect the development of left ventricular (LV) hypertrophy and contractile dysfunction in response to pressure overload. We hypothesized that a low-carbohydrate/high-fat diet prevents LV hypertrophy and dysfunction compared with high-carbohydrate diets.. Rats were fed high-carbohydrate diets composed of either starch or sucrose, or a low-carbohydrate/high-fat diet, and underwent abdominal aortic banding (AAB) for 2 months. AAB increased LV mass with all diets. LV end-diastolic and systolic volumes and the ratio of the mRNA for myosin heavy chain beta/alpha were increased with both high-carbohydrate diets but not with the low-carbohydrate/high-fat diet. Circulating levels of insulin and leptin, both stimulants for cardiac growth, were lower, and free fatty acids were higher with the low-carbohydrate/high-fat diet compared with high-carbohydrate diets. Among animals that underwent AAB, LV volumes were positively correlated with insulin and LV mass correlated with leptin.. A low-carbohydrate/high-fat diet attenuated pressure overload-induced LV remodeling compared with high-carbohydrate diets. This effect corresponded to lower insulin and leptin concentrations, suggesting they may contribute to the development of LV hypertrophy and dysfunction under conditions of pressure overload.

Topics: Animals; Blood Pressure; Diet, Carbohydrate-Restricted; Dietary Carbohydrates; Dietary Fats; Disease Models, Animal; Hypertension; Hypertrophy, Left Ventricular; Insulin; Leptin; Male; Nutritional Status; Rats; Rats, Wistar; Risk Factors; Ultrasonography; Ventricular Dysfunction, Left

Obesity is independently associated with increased cardiovascular risk. However, since established obesity clusters with various cardiovascular risk factors, configuring the metabolic syndrome, the early effects of obesity on vascular function are still poorly understood. The current study was designed to evaluate the effect of early obesity on coronary endothelial function in a new animal model of swine obesity. As to method, juvenile domestic crossbred pigs were randomized to either high-fat/high-calorie diet (HF) or normal chow diet for 12 wk. Coronary microvascular permeability and abdominal wall fat were determined by using electron beam computerized tomography. Epicardial endothelial function and oxidative stress were measured in vitro. Systemic oxidative stress, renin-angiotensin activity, leptin levels, and parameters of insulin sensitivity were evaluated. As a result, HF pigs were characterized by abdominal obesity, hypertension, and elevated plasma lysophosphatidylcholine and leptin in the presence of increased insulin sensitivity. Coronary endothelium-dependent vasorelaxation was reduced in HF pigs and myocardial microvascular permeability increased compared with those values in normal pigs. Systemic redox status in HF pigs was similar to that in normal pigs, whereas the coronary endothelium demonstrated higher content of superoxide anions, nitrotyrosine, and NADPH-oxidase subunits, indicating increased tissue oxidative stress. In conclusion, the current study shows that early obesity is characterized by increased vascular oxidative stress and endothelial dysfunction in association with increased levels of leptin and before the development of insulin resistance and systemic oxidative stress. Vascular dysfunction is therefore an early manifestation of obesity and might contribute to the increased cardiovascular risk, independently of insulin resistance.

Topics: Animals; Blood Pressure; Capillary Permeability; Coronary Vessels; Dietary Fats; Dinoprost; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Hypertension; Intra-Abdominal Fat; Leptin; Lipids; Microcirculation; Nitric Oxide; Obesity; Oxidative Stress; Random Allocation; Superoxides; Swine; Tomography, X-Ray Computed; Vasoconstrictor Agents; Vasodilator Agents

We recently showed that diencephalic TRH may mediate the central leptin-induced pressor effect. Here, to study the role of TRH in obesity-induced hypertension (OIH), we used a model of OIH produced by a high-fat diet (HFD, 45 days) in male Wistar rats. After 4 wk, body weight and systolic arterial blood pressure (SABP) increased in HFD animals. Plasma leptin was correlated with peritoneal adipose tissue. Then, we treated OIH animals with an antisense oligodeoxynucleotide and small interfering (si)RNA against the prepro-TRH. Antisense significantly decreased diencephalic TRH content and SABP at 24 and 48 h posttreatment. Similar effects were observed with siRNA against prepro-TRH but for up to 4 wk. Conversely, vehicle, an inverted antisense sequence and siRNA against green fluorescence protein, produced no changes. SABP decrease seems to be owing to an inhibition of the obesity-enhanced sympathetic outflow but not to an alteration in thyroid status. Using a simple OIH model we demonstrated, for the first time, that central TRH participates in the hypertension induced by body weight gain probably through its well-known action on sympathetic activity. Thus the TRH-leptin interaction may contribute to the strong association between hypertension and obesity.

Topics: Animals; Blood Pressure; Body Weight; Hypertension; Leptin; Male; Metanephrine; Normetanephrine; Obesity; Oligodeoxyribonucleotides, Antisense; Prolactin; Protein Precursors; Random Allocation; Rats; Rats, Wistar; RNA, Small Interfering; Thyrotropin; Thyrotropin-Releasing Hormone; Thyroxine; Triiodothyronine

Risperidone has a relatively low risk of causing obesity and diabetes mellitus and is a first-line treatment for schizophrenia. The aim of the present study was to investigate glucose and lipid metabolism, and feeding-control parameters in schizophrenia patients treated with long-term risperidone monotherapy. Fifteen patients with paranoid-type schizophrenia who had been treated with risperidone and had Global Assessment of Function (GAF) scores >70 were selected and compared with healthy volunteers (n = 25). Single assessments of psychotic symptoms, side-effects, Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) score, bodyweight, body fat percentage and blood sampling were performed. Fasting blood glucose, insulin, hemoglobin A1c, homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol, triglyceride, high density lipoprotein (HDL)-, low density lipoprotein-cholesterol, adiponectin, prolactin and feeding-control parameters (ghrelin and leptin) were analyzed. The body fat percentage (P = 0.0018), body mass index (BMI) (P = 0.0150), fasting blood glucose (P = 0.0358), triglyceride (P = 0.0377), leptin (P = 0.0243), total ghrelin (P = 0.0067), active ghrelin (P = 0.0241) and prolactin (P < 0.0001) levels of patients treated with risperidone were significantly higher than those of healthy volunteers, while the HDL-cholesterol level (P = 0.0222) was significantly lower. Although the patients had very mild psychiatric symptoms and maintained functionally high levels, the glucose and lipid parameters were significantly impaired compared to healthy volunteers. A high level of plasma ghrelin might increase appetite, leading to exacerbation of metabolic impairment.

Topics: Adiponectin; Adult; Antipsychotic Agents; Body Composition; Body Mass Index; Cholesterol, HDL; Female; Ghrelin; Glucose; Humans; Hypertension; Leptin; Lipid Metabolism; Lipids; Male; Middle Aged; Peptide Hormones; Psychiatric Status Rating Scales; Risperidone; Schizophrenia; Weight Gain

Topics: Abdominal Fat; Acanthosis Nigricans; Adolescent; Atherosclerosis; Bone Diseases, Endocrine; Child; Fatty Liver; Ghrelin; Humans; Hyperandrogenism; Hypertension; Insulin; Insulin Resistance; Leptin; Obesity; Peptide Hormones; Phenotype; Satiation; Sleep Apnea Syndromes

Obesity has been suggested to have a detrimental impact on kidney structure and function, leading to focal glomerulosclerosis and hypertension. It is also associated with hyperleptinemia and elevated renal sympathetic nerve activity. Prenatal undernutrition promotes postnatal obesity, hypertension, and an altered renal structure and function. In this study, we examined the effects of prenatal nutrient restriction and juvenile obesity in sheep. We found that juvenile obesity led to chronic hyperleptinemia and reduced renal function as assessed by nuclear scintigraphy. Additional factors include hypertension, glomerulosclerosis, and increased kidney apoptosis. Prenatal undernutrition, synchronous with early kidney development, coupled postnatally with juvenile obesity had no effect on systemic pathophysiological sequalae associated with obesity per se. Hypertension, hyperleptinemia, and poor renal function were all observed in this group. All indices of renal pathology such as increased expression of proinflammatory cytokines, angiotensin II, glucocorticoid receptors, and increased apoptosis and glomerulosclerosis were entirely absent in obese prenatally undernourished offspring. Our data indicate that juvenile obesity per se leads to systemic hypertension and renal structural and functional pathology. Prenatal undernutrition effectively abolishes any renal histopathology associated with juvenile obesity.

Topics: Animals; Animals, Newborn; Apoptosis; Blood Pressure; Diet; Female; Glomerular Filtration Rate; Heart Rate; Hypertension; Kidney; Kidney Diseases; Leptin; Malnutrition; Obesity; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Sheep

To investigate the effects of prenatal exposure to lipopolysaccharide (LPS) on blood pressure and body weight of offspring in rats.. Sixteen healthy, pregnant rats were randomly divided into 2 groups. The rats in the LPS group were injected intraperitoneally with LPS (0.79 mg/kg) on the d 8, d 10, and d 12 of gestation. Those in the control group were only treated with normal saline. After delivery, all offspring were weighed and blood pressure was measured by the tailcuff method once every 2 weeks from the 6th to the 24th week. In the 15th week, their food intake was weighed every day. At the end of the 24th week, the rats were killed by decapitation. Abdominal adipose tissues were weighed, and the serum level of leptin was detected by radioimmunoassay.. The offspring with prenatal LPS exposure showed increased systemic arterial pressure, heavier body weight, elevated food intake, increased adipose tissue weight, and increased circulating leptin compared with the controls.. Prenatal exposure to LPS leads to increases in blood pressure and body weight in rats.

Topics: Adipose Tissue; Animals; Blood Pressure; Body Weight; Eating; Female; Fetus; Humans; Hypertension; Leptin; Lipopolysaccharides; Male; Pregnancy; Prenatal Exposure Delayed Effects; Random Allocation; Rats; Rats, Sprague-Dawley

This study examined the effect of leptin on renal ouabain-resistant Na(+)-ATPase, which drives the reabsorption of about 10% of sodium transported in the proximal tubule. Chronic leptin administration (0.25 mg/kg s.c. twice daily for seven days) increased Na(+)-ATPase activity by 62.9%. This effect was prevented by the coadministration of superoxide dismutase mimetic, tempol, or the NADPH oxidase inhibitor, apocynin (2 mM in the drinking water). Acutely administered NO donors decreased Na(+)-ATPase activity. This effect was abolished by soluble guanylate cyclase inhibitor, ODQ, but not by protein kinase G inhibitors. Exogenous cGMP reduced Na(+)-ATPase activity, but its synthetic analogues, 8-bromo-cGMP and 8-pCPT-cGMP, were ineffective. The inhibitory effect of NO donors and cGMP was abolished by EHNA, an inhibitor of cGMP-stimulated phosphodiesterase (PDE2). Exogenous cAMP analogue and dibutyryl-cAMP increased Na(+)-ATPase activity and abolished the inhibitory effect of cGMP. Finally, the administration of superoxide-generating mixture (xanthine oxidase+hypoxanthine) increased Na(+)-ATPase activity. The results suggest that nitric oxide decreases renal Na(+)-ATPase activity by stimulating cGMP, which in turn activates PDE2 and decreases cAMP concentration. Increased production of reactive oxygen species may lead to the elevation of Na(+)-ATPase activity by scavenging NO and limiting its inhibitory effect. Chronic hyperleptinemia is associated with increased Na(+)-ATPase activity due to excessive oxidative stress.

Topics: Adenosine Triphosphatases; Animals; Cation Transport Proteins; Disease Models, Animal; Enzyme Inhibitors; Free Radical Scavengers; Hypertension; Kidney Tubules, Proximal; Leptin; Male; Nitric Oxide; Nucleotides, Cyclic; Obesity; Ouabain; Rats; Rats, Wistar; Sodium-Potassium-Exchanging ATPase

This study evaluated the effect of chronic sucrose feeding on hemodynamic parameters and renal sympathetic nervous activity. In addition, angiotensin I, II, and 1-7 levels were determined in plasma, heart, kidney, and the epididymal adipose tissue.. Male Wistar rats were treated for 30 days with 20% sucrose solution (n = 21) or tap water (n = 19) and food ad libitum. Blood pressure, cardiac output, and total peripheral resistance were recorded at the end of the 30-day treatment period. Sympathetic and angiotensinergic systems were evaluated by acute hexamethonium and captopril administration; plasma and tissue (heart, kidney, and epididymal adipose tissue) angiotensins were measured by high-performance liquid chromatography; and angiotensin-converting enzyme activity was determined by continuous fluorescent assay. Plasma renin activity and plasma levels of insulin and leptin were evaluated by radioimmunoassay.. Chronic sucrose feeding was associated with increased blood pressure (BP) (129 +/- 1 v 102 +/- 3 mm Hg) and circulating insulin (171%) and leptin (356%) levels when compared with the control group. The sucrose group also showed a 27% higher renal sympathetic nervous activity. The depressor response to hexamethonium was similar in both groups, whereas captopril caused a more pronounced decrease in BP in the sucrose group than in controls (-40 +/- 2 v -11 +/- 2 mm Hg), possibly reflecting the higher plasma renin activity and plasma content of angiotensin II and renal angiotensin II in sucrose rats.. These findings suggest a specific renal renin-angiotensin-sympathetic activation as a potential mechanism for the cardiovascular changes in response to chronic sucrose feeding.

Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Animals; Blood Pressure; Body Weight; Captopril; Cardiac Output; Dietary Sucrose; Hexamethonium; Hypertension; Insulin; Kidney; Leptin; Male; Random Allocation; Rats; Rats, Wistar; Renin; Renin-Angiotensin System; Sodium; Sympathetic Nervous System; Vascular Resistance

The present study aimed to evaluate the effects of a post-weaning high-fat (HF) diet upon hepatic morphology in rats subjected to perinatal protein restriction. Pregnant Wistar rats were assigned to a normal-protein diet (NP; with 19 % of protein) or a low-protein (LP) diet (with 5 % of protein). At weaning, the following groups were formed: NP and NP-HF, males and females, which were fed standard chow and an HF diet, respectively. Likewise, LP rat dams originated LP and LP-HF offspring, both sexes. Euthanasia was performed at 6 months of age. Three-way ANOVA disclosed a three-factor interaction among sex, perinatal diet and HF diet in relation to body mass, retroperitoneal fat pad, liver mass:tibia length ratio, binucleation rate and hepatocyte area at 6 months old (P < 0.05). The high-fat diet intensified the effects of perinatal protein restriction concerning systolic blood pressure, genital fat pad and hepatocyte number (P < 0.05; two-way ANOVA). Furthermore, higher steatosis rates and insulin and leptin concentrations were found in males fed on the HF diet, indicating a sex-post-weaning diet interaction (P < 0.05; two-way ANOVA). Fetal programming and HF diet as a single stimulus caused mild hypertension at 3 months, an important reduction in hepatocyte number as well as stage 1 steatosis at 6 months. However, hypertension and hepatocyte number deficit were worsened and grade 2 steatosis occurred after exposure to the HF diet. All of these serve to highlight the paramount importance of intra-uterine conditions and postnatal diet quality when it comes to the pathogenesis of chronic diseases.

Topics: Animals; Diet, Protein-Restricted; Dietary Fats; Fatty Liver; Female; Hypertension; Insulin; Leptin; Liver; Male; Pregnancy; Prenatal Exposure Delayed Effects; Prenatal Nutritional Physiological Phenomena; Rats; Rats, Wistar; Sex Factors; Weaning

Obesity and high blood pressure (BP) commonly coexist in patients, and both conditions are associated with elevated sympathetic nervous activity. We tested whether the sympathetic nervous system was differently affected in men and women by the body mass index (BMI), BP, leptin and weight loss.. We measured muscle sympathetic nerve activity (MSNA, microneurography), BP and plasma leptin concentrations in 167 age-matched normotensive and hypertensive men and women divided into three subgroups: lean, BMI < 25 kg/m; overweight, BMI > or = 25 and < 30 kg/m; and obese, BMI > or = 30 kg/m. These measurements were repeated in a subgroup of 19 obese subjects who underwent a 12-week diet.. Women with hypertension had increased MSNA compared with their normotensive counterparts (37 +/- 2 versus 25 +/- 2 bursts/min, analysis of variance, P < 0.001) and MSNA was significantly related to BP (P < 0.05, r = 0.236) but not to BMI. MSNA in men with hypertension was no different from that in normotensive subjects (33 +/- 2 versus 30 +/- 2 bursts/min), but MSNA was significantly related to BMI (P < 0.05, r = 0.249). Diet resulted in the same degree of weight loss in men and women, but induced a decrease in MSNA only in men (43 +/- 3 to 34 +/- 3 bursts/min, P < 0.01). The plasma leptin concentration was higher in women than in men, and for both groups it was related to BMI not BP (r = 0.497, P < 0.001 in women and r = 0.483, P < 0.001 in men).. These data demonstrate a gender difference in the regulation of the sympathetic nervous system, in which MSNA mainly relates to BP in women and to BMI in men.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Muscle, Skeletal; Neural Conduction; Neurology; Obesity; Sex Factors; Sympathetic Nervous System; Weight Loss

Leptin, homocysteine (Hcy), and C-reactive protein are risk factors potentially useful in predicting future cardiac events. These plasma biomarkers may participate in the regulation of cardiovascular function through an NO-dependent mechanism. Our purpose was to investigate whether alterations in C-reactive protein, Hcy, leptin, and NO are present in small-for-gestational-age children and to determine whether the levels of these plasma biomarkers are associated with birth weight, vascular function, and blood pressure. Concentrations of leptin, Hcy, C-reactive protein, and NO were measured in 69 children (36 boys and 33 girls; ages 8 to 13 years). Leptin (means difference: 1.4 ng/mL; 95% CI: 0.4 to 2.4) and Hcy (means difference: 0.9 micromol/L; 95% CI: 0.3 to 1.5) levels were significantly elevated in children born small for gestational age compared with those with appropriate birth weight. Nevertheless, NO (means difference: 342.9 micromol; 95% CI: 124.2 to 561.6) concentration was significantly reduced in small birth weight children, and the levels of C-reactive protein remained unchanged. There was a significant association between the circulating levels of both NO and Hcy with vascular function, as well as with blood pressure levels, in our population. Because both Hcy and NO are associated with a risk of cardiovascular disease, it is possible that part of the association of low birth weight with elevated risk for vascular and metabolic disease in later life is mediated by perturbation in pathways for these biomarkers.

Topics: Adolescent; Age Distribution; Biomarkers; Blood Pressure; C-Reactive Protein; Cardiovascular Physiological Phenomena; Child; Cohort Studies; Confidence Intervals; Female; Follow-Up Studies; Homocysteine; Humans; Hypertension; Incidence; Infant, Newborn; Infant, Small for Gestational Age; Leptin; Male; Nitric Oxide; Probability; Reference Values; Risk Assessment; Sex Distribution; Term Birth

The objective of this research was to examine the contribution of a moderately high fat (MHF) diet to the development of salt-sensitive hypertension in obese Zucker rats. Lean and obese Zucker rats were fed either a MHF diet or a diet of standard rat chow (control diet) for 10 weeks. From week 4 through week 10, the drinking water was supplemented with 1% NaCl. Blood pressure was measured weekly, and urinary excretion of nitric oxide metabolites (NO(x)) was determined at weeks 4 and 10. At week 10, renal nitric oxide synthase (NOS) activity was assessed in kidney homogenates. Blood pressures of obese, but not lean, rats on the MHF fat diet were significantly increased by salt-supplementation, whereas blood pressures of rats on the control diet were not appreciably affected. NO(x) excretion was increased in response to salt-supplementation in rats on the control diet, with the effect being particularly dramatic in obese rats. After salt-supplementation, NO(x) excretion by rats on the MHF diet was lower than rats on the control diet. In obese rats on the MHF diet, this decrease in NO production was accompanied by a reduction in renal NOS activity. These results indicate that obese rats are more inclined than lean rats to develop diet-induced hypertension in response to a moderately high fat, salt-supplemented diet. Furthermore, they suggest that MHF diet-induced defects in NO production may promote the salt-sensitivity of blood pressure in obese Zucker rats, which appear to require more NO to maintain blood pressure during a salt challenge.

Topics: Animals; Body Weight; Diet; Dietary Fats; Disease Models, Animal; Feedback, Physiological; Female; Hypertension; Insulin; Leptin; Nitrates; Nitric Oxide; Nitric Oxide Synthase; Nitrites; Nutrition Disorders; Obesity; Rats; Rats, Zucker; Sodium Chloride, Dietary

Leptin and/or ghrelin, initially thought to be considered messengers of energy metabolism, are now considered to play a role in normal and complicated pregnancy. In this study, pregnant, spontaneously hypertensive rats (SHR) have been used to evaluate, for the first time, the modification of leptin and ghrelin both at serum and tissue levels. In SHR, we evaluate plasma leptin level and tissue protein expression in both placenta and adipose tissue at the end of gestation (day 20) versus normotensive Wistar-Kyoto (WKY) animals. The expression of functional leptin receptor (Ob-Rb) in peripheral tissues and in the hypothalamus was evaluated. Moreover, we measured plasma ghrelin level and its mRNA expression in the stomach and placenta. SHR strain presented significantly lower plasma leptin levels when compared with those found in pregnant or not WKY controls. Interestingly, in the placenta, leptin gene expression was higher in SHR than normotensive WKY. Moreover, we demonstrated a resistance to the effects of leptin via 'downregulation' of hypothalamic receptors in pregnant SHR. Conversely, SHR presented significantly higher ghrelin plasma levels when compared with those found in pregnant or not WKY. However, we observed that ghrelin level in the stomach of SHR did not change during pregnancy, and on the opposite, mRNA ghrelin in the placenta of SHR was lower than that of normotensive rats, suggesting a different production of this hormone in the fetal-placental unit. These data gain further insight into metabolic hormone modifications observed in a model of pre-existing hypertension associated with pregnancy.

Topics: Adaptation, Physiological; Adipose Tissue; Animals; Female; Gene Expression; Ghrelin; Hypertension; Hypothalamus; Leptin; Models, Animal; Obesity; Placenta; Pregnancy; Pregnancy Complications, Cardiovascular; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach

The orexigenic hormone ghrelin induces weight gain by stimulating food intake. Ghrelin has been shown to modulate sympathetic activity, to exert vasodilative effects and to counterreact with leptin on both food intake and blood pressure. Of these two hormones, ghrelin levels are decreased in obesity, whereas leptin levels are increased. In this cross-sectional study, differences in serum ghrelin and leptin levels were examined in normotensive and hypertensive obese women.. Sixty-one normotensive and hypertensive women were classified according to the body mass indices as follows: (a) 18 healthy subjects with BMI 21.5-27.5 kg/m(2); (b) 22 normotensive subjects with BMI 30-47 kg/m(2); (c) 21 hypertensive obese subjects (BMI 30-48 kg/m(2)) with systolic blood pressure > or =140 mmHg or diastolic blood pressure > or =90 mmHg. Anthropometric measurements including height, weight, BMI, waist and hip circumferences and blood pressure were recorded. The levels of ghrelin and leptin were determined in sera using the commercial ELISA kits.. In normotensive obese subjects, ghrelin levels were significantly lower than in controls (0.21+/-0.13 vs 0.60+/-0.3 ng/mL), whereas hypertensive obese women had elevated ghrelin levels (0.64+/-0.36 ng/mL). Ghrelin concentration was decreased despite the presence of hypertension in the patients who had BMIs above 35 kg/m(2). Leptin levels were significantly higher in both normotensive and hypertensive obese groups (19.54+/-11.19 and 21.61+/-12.7 ng/mL, respectively) than in controls (7.61+/-3.3 ng/mL), and were not affected by the presence of hypertension in obese subjects.. Ghrelin was positively associated with hypertension in obese women and this association was inversely influenced by the increase of BMI.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Cross-Sectional Studies; Female; Ghrelin; Growth Hormone; Humans; Hypertension; Leptin; Middle Aged; Obesity; Peptide Hormones; Postmenopause; Turkey

The present study employed a rat leptin antagonist to evaluate the role of elevated leptin in obesity-associated hypertension.. First, leptin was overexpressed in the hypothalamus of lean rats for 155 days through the administration of a recombinant adeno-associated viral-mediated central vector-encoding leptin. Then a leptin antagonist was infused intracerebroventricularly for 14 days. In a second experiment, rats were fed with a high-fat diet or chow for 5 months, then the leptin antagonist was infused intracerebroventricularly for 14 days.. Hypothalamic overexpression of leptin elevated blood pressure by 18 mmHg, but 14-day central infusion of the leptin antagonist reversed leptin-induced hypertension. High-fat feeding increased blood pressure (by approximately 8-9 mmHg) and tyrosine hydroxylase activity (by 76%) in superior cervical ganglia compared with chow feeding. Leptin antagonist infusion accelerated weight gain, food intake, and adiposity in high-fat-fed rats compared with chow-fed rats, and tyrosine hydroxylase activity was also reversed in the superior cervical ganglia. Elevated mean arterial pressure was not affected, although there was a small decrease in heart rate in both chow and high-fat-fed groups.. Central overexpression of leptin leads to hypertension that can be reversed by a leptin antagonist. In contrast, this leptin antagonist does not reverse the high-fat feeding-induced elevation of blood pressure, even though there is apparent blockade of other leptin-mediated metabolic and sympatho-excitatory responses.

Topics: Animals; Dependovirus; Dietary Fats; Gene Expression; Genetic Vectors; Hypertension; Hypothalamus; Injections, Intraventricular; Leptin; Male; Mutagenesis, Site-Directed; Obesity; Phosphorylation; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Recombinant Proteins; Signal Transduction; STAT3 Transcription Factor

Fetal programming is now recognized as a key determinant of the adult phenotype, with major implications for adult-onset diseases including hypertension. Two mediators of fetal programming are maternal nutrition and fetal glucocorticoid exposure. Recent studies show that postnatal dietary manipulations can exacerbate programming effects, but whether programming effects can be attenuated by postnatal dietary manipulations, and thus provide a possible therapeutic strategy, is unknown. In this study, we tested the hypothesis that a postnatal diet enriched with long-chain omega-3 fatty acids attenuates programmed hyperleptinemia and hypertension. Pregnant rats were treated with dexamethasone (Dex) from d 13 to term, and offspring were cross-fostered to mothers on either a standard diet or a diet high in omega-3 fatty acids and remained on these diets postweaning. Maternal Dex reduced birthweight and delayed the onset of puberty in offspring. Hyperleptinemia (associated with elevated leptin mRNA expression in adipose tissue) and hypertension were evident in offspring by 6 months of age in Dex-exposed animals consuming a standard diet, but these effects were completely blocked by a high omega-3 diet. These results demonstrate for the first time that manipulation of postnatal diet can limit adverse outcomes of fetal programming, with programmed hyperleptinemia and hypertension prevented by a postnatal diet enriched with omega-3 fatty acids. This raises the possibility that dietary supplementation with omega-3 fatty acids may provide a viable therapeutic option for preventing and/or reducing adverse programming outcomes in humans.

Topics: Animals; Animals, Newborn; Body Weight; Dietary Fats; Energy Intake; Fatty Acids, Omega-3; Female; Hyperlipidemias; Hypertension; Leptin; Male; Pregnancy; Pregnancy, Animal; Rats; Rats, Wistar

No data have been so far reported on the relationship between polymorphisms of LEP gene and cardiovascular disease.. We genotyped a tetranucleotide repeat mapped in the 3'UTR of the LEP gene (LEP-tet) in 109 subjects with cardiovascular events and in 109 control subjects.. Univariate analysis and multivariate logistic regression analysis adjusted for age, gender, smoking status, history of hyperlipidemia, hypertension or diabetes showed not significant association between the genotype of the LEP-tet and cardiovascular diseases. Moreover, no differences were observed in the plasma leptin concentrations between cases and control subjects (22 +/- 19 vs 22 +/- 14 ng/ml, P = 0.52) and in relation to the LEP-tet classes or carriage of specific alleles (P = 0.76 for the association between LEP-tet classes and leptin levels in overall analysis).. In conclusion, our data do not support an association between the LEP-tet microsatellite polymorphism of the human LEP gene and cardiovascular diseases.

Topics: 3' Untranslated Regions; Age Factors; Aged; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Hypertension; Leptin; Logistic Models; Male; Microsatellite Repeats; Middle Aged; Polymorphism, Genetic; Sex Factors; Smoking

We evaluated the relationship of leptin with hypertension adjusted for body mass index (BMI) and/or waist circumference in a population of Japanese-Brazilian women aged > or = 30 years with centrally distributed adiposity. After excluding diabetic subjects, the study subjects--who participated in a population-based study on the prevalence of metabolic syndrome--showed prevalence rates of obesity (BMI > or = 25 kg/m2) and central adiposity (waist > or = 80 cm) of 32.0 and 37.8%, respectively. The hypertensive group (N = 162) was older, had higher BMI (24.9 +/- 4.2 vs 23.3 +/- 3.4 kg/m2, P < 0.001), waist circumference (81.1 +/- 10.1 vs 76.3 +/- 8.2 cm, P < 0.001) and insulin levels (8.0 +/- 6.2 vs 7.1 +/- 4.9 microU/mL, P < 0.05) than the normotensive group (N = 322) and showed an unfavorable metabolic profile (higher 2-h plasma glucose, C-reactive protein and non-HDL cholesterol levels). Leptin did not differ between groups (8.2 +/- 6.8 vs 7.2 +/- 6.6 ng/mL, P = 0.09, for hypertensive vs normotensive, respectively) and its levels correlated significantly with anthropometric variables but not with blood pressure. Logistic regression analysis indicated that age and waist were independently associated with hypertension but not with homeostasis model assessment of insulin resistance or leptin levels. The lack of an independent association of hypertension with metabolic parameters (2-h glucose, C-reactive protein and non-HDL cholesterol) after adjustment for central adiposity suggested that visceral fat deposition may be the common mediator of the disturbances of the metabolic syndrome. Our data indicate that age and waist are major determinants of hypertension in this population of centrally obese (waist > or = 80 cm) Japanese-Brazilian women, but do not support a role for leptin in the elevation of blood pressure.

Topics: Abdominal Fat; Adult; Body Mass Index; Brazil; C-Reactive Protein; Cholesterol; Female; Humans; Hypertension; Insulin; Japan; Leptin; Logistic Models; Middle Aged; Obesity; Waist-Hip Ratio

Ghrelin is a recently discovered protein hormone mainly synthesized in the gastric endocrine cells. This hormone not only is a potent growth hormone secretagogue but also is involved in the regulation of food ingestion and energy metabolism. Derangements in ghrelin secretion in patients with chronic renal failure (CRF) have not been fully evaluated.. Our aim has been to quantify serum concentrations of total ghrelin in a group of patients with CRF on chronic therapy with both haemodialysis (HD) and peritoneal dialysis (PD) in comparison with a group of patients on conservative management (predialysis).. We studied 68 CRF patients treated by HD (n = 30, 16 men, age 61.2 +/- 1.8 years) and PD groups (n = 38, 21 men, age 54.4 +/- 1.7 years). A group of 19 uraemic patients on conservative management served as the control. Serum concentrations of ghrelin, leptin, insulin, IGF I and GH were measured in all subjects.. Patients undergoing HD showed similar concentrations of ghrelin in comparison with the control group (9491 +/- 787 vs 9280 +/- 918 pg/ml, NS). However, PD patients exhibited baseline ghrelin concentrations significantly lower than those found in patients on conservative management (3230 +/- 216 pg/ml, P < 0.0001). Men and women showed similar serum ghrelin levels in both HD (9845.9 +/- 1071 vs 9085 +/- 1194 pg/ml) and PD patients (3214 +/- 297 vs 3250 +/- 324 pg/ml). Hypertension and diabetes mellitus did not influence ghrelin levels. Serum GH levels were positively correlated with serum ghrelin concentrations in both HD (r = 0.46, P < 0.05) and PD (r = 0.53, P < 0.001) patients; however, no relationships between ghrelin, leptin, insulin and IGF I were found.. These results suggest that PD is accompanied by a striking decrement in baseline ghrelin concentrations in comparison with values found both in HD and control patients. Further studies are necessary to determine mechanisms involved in ghrelin regulation in uraemic patients.

Topics: Adult; Case-Control Studies; Diabetes Complications; Erythropoietin; Female; Ghrelin; Growth Hormone; Humans; Hypertension; Insulin; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Leptin; Lipids; Male; Middle Aged; Peptide Hormones; Peritoneal Dialysis; Recombinant Proteins; Regression Analysis; Renal Dialysis

A previous study of ours demonstrated that a high-fat diet (FAT) causes body fat accumulation, as well as elevation of plasma leptin level, renal sympathetic nerve activity (RSNA), and blood pressure (BP). In the study reported here, we analyzed the role of leptin in these elevations of the RSNA and BP due to FAT feeding by assessing sympathetic and cardiovascular responses to intravenous (IV) administration of leptin in rats fed either a FAT or a high-carbohydrate diet (CHO). The results showed that baseline body fat, plasma leptin level, RSNA and BP were significantly higher in the FAT group than in the CHO group, and that IV administration of leptin elevated RSNA and plasma leptin levels but lowered BP in the CHO group. However, these effects of leptin were eliminated in the FAT group. These findings suggest that FAT-fed rats which expose basal elevation of plasma leptin levels, RSNA and BP might be hyposensitive to endogenous leptin. Therefore, leptin resistance appeared obviously in FAT-induced hypertension might indicate that leptin is implicated in generating the elevation of RSNA and BP induced by long-term FAT feeding.

Topics: Animals; Blood Pressure; Dietary Carbohydrates; Dietary Fats; Hypertension; Infusions, Intravenous; Kidney; Leptin; Male; Rats; Rats, Sprague-Dawley; Sympathetic Nervous System

Previous investigations in normotensive animals have demonstrated a marked natriuretic and diuretic response following the acute administration of supraphysiologic doses of synthetic leptin. However, the importance of endogenous leptin in the regulation of renal sodium and water balance is not yet defined. This study examined the hemodynamic and renal excretory effects of circulating leptin blockade with a specific polyclonal antibody in groups of normotensive, chronically saline-loaded Sprague-Dawley rats. In the experimental group (n = 10), leptin antibody significantly decreased urinary sodium excretion and urinary flow by approximately 30% compared to the control rats (n = 10). Mean arterial pressure remained unchanged. Collectively, these results are interpreted to suggest that leptin is an important renal sodium-regulating factor under conditions of mild sodium and volume expansion.

Topics: Animals; Blood Pressure; Homeostasis; Hypertension; Kidney; Leptin; Male; Natriuresis; Rats; Rats, Sprague-Dawley; Renal Circulation; Sodium; Sodium Chloride

Studies have demonstrated that high serum leptin levels are associated with aging. However, we do not know whether hyperleptinemia is a relevant risk factor for high blood pressure (HBP) in the elderly.. To determine the relationship between hyperleptinemia and HBP in the elderly.. A comparative cross-sectional study was carried out in a convenience sample of 70 healthy elderly persons comprising 46 women (mean age, 67 +/- 5.8 years) and 24 men (mean age, 73 +/- 7.5 years), and a group of 91 elderly persons with HBP, comprising 62 women (mean age, 67 +/- 8.2 years) and 29 men (mean age, 70 +/- 0.3 years). We measured serum leptin levels through the radioimmunoassay method.. The elderly subjects with HBP had significantly higher leptin levels than the healthy elderly subjects (P = .02). Furthermore, in female elderly subjects we observed a statistically significant correlation between systolic blood pressure and leptin (r = 0.37, P = .003), as well as systolic blood pressure and age (r = 0.29, P = .02), but not with diastolic blood pressure. In male elderly subjects, there was no correlation between leptin and systolic blood pressure or leptin and diastolic blood pressure. However, hyperleptinemia as risk factor for HBP was nearly 5 times higher in men than in women (men, odds ratio = 18.0, 95% confidence interval 3.2-100.9, P < .001 vs women, odds ratio = 3.33, 95% confidence interval 1.4-7.4, P = .003).. Our data suggest that hyperleptinemia was a significant risk factor for HBP elderly individuals, mainly in men.

Topics: Age Factors; Aged; Blood Pressure; Body Constitution; Body Mass Index; Cross-Sectional Studies; Female; Humans; Hypertension; Leptin; Male; Mexico; Odds Ratio; Risk Factors

We explored the mechanisms underlying the close association between hypertension and insulin resistance by measuring the changes in the plasma levels of adiponectin, a novel insulin sensitizer secreted by adipose tissue, in rats infused with angiotensin II (AII). Angiotensin II (100 ng/kg per minute) was subcutaneously infused with osmotic minipumps for 2 weeks in rats fed with either standard chow or a high-fructose diet. Insulin sensitivity index (SI) was assessed by the minimal model of Bergman [Diabetes 1989;38:1512-27]. Angiotensin II infusion significantly increased blood pressure and decreased SI. Angiotensin II decreased plasma adiponectin levels from 3.7 to 2.9 microg/mL (P < .01) without affecting the expression of adiponectin messenger RNA in adipose tissue. Angiotensin II infusion did not affect plasma leptin and tumor necrosis factor alpha levels. An AII type 1 receptor blocker, olmesartan, restored the low adiponectinemia induced by the AII infusion (50 ng/kg per minute). Plasma adiponectin levels were significantly lower in fructose-fed rats (2.3 microg/mL) than in chow-fed rats. Angiotensin II induced no further decrease of adiponectin, whereas olmesartan increased adiponectin remarkably both with and without AII infusion. The AII type 2 receptor blocker PD123319 left the AII-induced hypoadiponectinemia unchanged in both chow- and fructose-fed rats. The AII type 2 receptor agonist CGP42112A also left the adiponectin unchanged. Plasma adiponectin levels were substantially correlated with SI (r = 0.61, P < .0001). These results suggest that AII suppresses adiponectin production via AII type 1 receptor, resulting in impaired insulin sensitivity.

Topics: Adiponectin; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin II Type 2 Receptor Blockers; Animals; Blood Glucose; Dose-Response Relationship, Drug; Glucose Tolerance Test; Hypertension; Imidazoles; Injections, Subcutaneous; Insulin; Insulin Resistance; Leptin; Male; Oligopeptides; Pyridines; Rats; Rats, Wistar; Receptors, Adiponectin; Receptors, Cell Surface; Tetrazoles; Tumor Necrosis Factor-alpha

Perivascular adipose tissue of normotensive rats releases a transferable factor that induces relaxation by opening voltage-dependent K+ (Kv) channels. The relevance of these observations to hypertension is unknown.. We characterized mesenteric perivascular adipose tissue from 3-month-old Wistar Kyoto rats (WKY) and aged-matched spontaneously hypertensive rats (SHR). Mesenteric bed (MB) weight and MB total lipid content were lower in SHR than in WKY. Freshly isolated MB adipocytes were smaller in SHR. Plasma triglycerides, glycerol, nonesterified free-fatty acids, and cholesterol were also lower in SHR. Plasma and mesenteric leptin were correlated with the quantity of mesenteric fat. To study vascular function, the MB was cannulated and perfused at a constant 2 mL/min flow. The Kv channel blocker 4-aminopyridine (4-AP; 2 mmol/L) increased perfusion pressure less in SHR MB than WKY and was directly correlated with the mesenteric fat amount. In isolated mesenteric artery rings, 4-AP (2 mmol/L) induced a contractile effect that was attenuated in SHR compared with WKY. The anticontractile effects of perivascular fat were reduced in SHR mesenteric artery rings compared with WKY.. Differences in visceral perivascular adipose tissue mass and function may contribute to the increased vascular resistance observed in SHR.

Topics: 4-Aminopyridine; Adipocytes; Adipose Tissue; Animals; Blood Vessels; Cell Size; Hypertension; In Vitro Techniques; Leptin; Lipids; Male; Mesenteric Arteries; Potassium Channel Blockers; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Splanchnic Circulation; Vasoconstriction; Vasomotor System

Previously, we found that bis(allixinato)oxovanadium(IV) (VO(alx)(2)) exhibits a potent hypoglycemic activity in type 1-like diabetic mice. Since the enhancement of insulin sensitivity is involved in one of the mechanisms by which vanadium exerts its anti-diabetic effects, VO(alx)(2) was further tested in type 2 diabetes with low insulin sensitivity. The effect of oral administration of VO(alx)(2) was examined in obesity-linked type 2 diabetic KKA(y) mice. Treatment of VO(alx)(2) for 4 weeks normalized hyperglycemia, glucose intolerance, hyperinsulinemia, hypercholesterolemia and hypertension in KKA(y) mice; however, it had no effect on hypoadiponectinemia. VO(alx)(2) also improved hyperleptinemia, following attenuation of obesity in KKA(y) mice. This is the first example in which a vanadium compound improved leptin resistance in type 2 diabetes by oral administration. On the basis of these results, VO(alx)(2) is proposed to enhance not only insulin sensitivity but also leptin sensitivity, which in turn improves diabetes, obesity and hypertension in an obesity-linked type 2 diabetic animal.

Topics: Animals; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Hypertension; Insulin Resistance; Leptin; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Models, Chemical; Obesity; Organometallic Compounds; Tissue Distribution

Recent evidence suggested that leptin-induced oxidative stress in human endothelial cells in vivo and increased oxidative stress in human essential hypertension may further contribute to both the development of atherosclerosis and other cardiovascular diseases. We investigated the association of plasma leptin levels with plasma lipid peroxidation and nitric oxide metabolites (NOx) in obese hypertensive atherosclerosis model.. Plasma leptin, lipid peroxidation and NOx levels were determined in age-matched non-obese normotensive female subjects (n = 30), obese normotensive female subjects (n = 45), and obese hypertensive female subjects (n = 50). Plasma leptin levels were determined by immunoradiometric method. Lipid peroxidation was determined as thiobarbituric acid reactive substances (TBARS) using spectrophotometric method. NOx levels were determined using enzymatic method.. We found that plasma leptin and TBARS levels were increased in obesity, and obese hypertensives have significantly higher plasma leptin and TBARS levels than obese normotensives (p <0.001 and p <0.001). Obese hypertensives have significantly lower plasma NOx levels than obese normotensives (p <0.001). In univariate and multivariate regression analysis, plasma leptin levels were significantly correlated with TBARS (p <0.01 and p <0.01) in obese subjects. Plasma TBARS were also inversely correlated with NOx in hypertensive obese subjects (r = -0.412, p <0.01).. Our results have shown that elevated leptin levels may be associated with increased oxidative stress and free-radical-induced decreased NOx levels. Therefore, hyperleptinemia may be an important contributor to the generation of hypertension in obesity.

Topics: Atherosclerosis; Female; Humans; Hypertension; Leptin; Lipid Peroxidation; Middle Aged; Nitric Oxide; Obesity; Oxidative Stress

Topics: Blood Pressure; Humans; Hypertension; Leptin; Obesity

Growing evidence suggests that concentration of the adipocytokines leptin and adiponectin may be affected by risk of hypertension during pregnancy. Leptin and leptin receptor gene expression has been studied in placentas obtained from pre-eclamptic patients, but not in those with chronic high blood pressure (CHBP). Adiponectin receptors remain unstudied in placentas obtained from hypertensive patients.. Therefore, we investigated relative mRNA expression of selected adipocytokine genes (leptin, leptin receptors (LEPRA, LEPRB, LEPRC, LEPRD) and adiponectin receptors (ADIPOR1, ADIPOR2)) in placental tissues from women with pre-eclampsia (n = 6) or CHBP (n = 8). Placentas from 28 normotensive patients were analyzed as controls. mRNA extracted from biopsies taken from the maternal and fetal sides of the placenta was investigated using real-time polymerase chain reaction.. Compared with controls, significant increases in leptin mRNA expression were seen in placentas from pre-eclamptic patients on the maternal (p = 0.01) and fetal (p = 0.02) sides, and in placentas from CHBP mothers on the fetal side (p = 0.001). Maternal-side tissue from CHBP patients was not significantly different from that of controls (p = 0.08), but this might be due to the small sample size. No significant differences were seen in mRNA expression for most of the adipocytokine receptors tested for hypertensive cases compared with controls. However, there was a decrease in LEPRC (pre-eclamptic, maternal side, p = 0.03) and LEPRD (pre-eclamptic, maternal side, p = 0.01; CHBP, fetal side, p = 0.009) in case-control analysis.. This pilot study shows that increases seen in leptin expression in placentas from hypertensive mothers might be a consequence of defects in placentation associated with this disease, and motivates further region-specific adipocytokine gene expression analysis across this organ.

Topics: Adult; Chronic Disease; Cytokines; Female; Gene Expression; Humans; Hypertension; Leptin; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Receptors, Adiponectin; Receptors, Cell Surface; Receptors, Leptin; RNA, Messenger

To measure serum leptin levels and compare them in lean and obese subjects and to identify correlation between serum leptin levels, heart rate and hypertension in lean and obese subjects among adult females.. A case control study.. Jinnah Medical and Dental College Hospital's Outpatient Department (OPD) during the calender year 2003.. Seventy female subjects with different body mass indices were selected from OPD of Jinnah Medical and Dental College Hospital (OPD), Karachi. Heart rate was counted manually; blood pressure was measured by mercury sphygmomanometer while serum leptin was measured using enzyme-linked immunoassay. The outcomes hypertension and heart rate were correlated to risk factor leptin.. Mean heart rate, systolic and diastolic blood pressure and serum leptin levels of obese people were 90 +/- 1, 142 +/- 2, 89 +/- 1 and 24.13 +/- 1.7 respectively, which were significantly higher as compared to lean subjects (p<0.05). All the parameters correlated positively and significantly with increasing BMI.. There was a relationship of tachycardia and hypertension with high serum leptin levels in obesity. Serum leptin levels increase with the level of obesity. Hyper-leptinemia is associated with tachycardia and increases in both systolic and diastolic blood pressure in obesity via complex mechanisms.

Topics: Adult; Body Mass Index; Cross-Sectional Studies; Female; Humans; Hypertension; Leptin; Middle Aged

Topics: Erythrocyte Membrane; Humans; Hypertension; Leptin; Membrane Fluidity; Receptors, Cell Surface; Receptors, Leptin

Leptin attenuates the angiotensin II-induced increase of cytosolic calcium ([Ca2+]i) and vasoconstriction in the aorta of normotensive Wistar rats. To determine whether these effects may be altered in hypertension, we assessed the effect of leptin on angiotensin II-induced vascular response in the aorta of 10-week-old spontaneously hypertensive rats (SHR).. Contractile responses to angiotensin II (100 nmol/l) in the presence of different concentrations of leptin (0.1, 1, 10, 100 nmol/l) were evaluated in isolated aortic rings by the organ bath system. [Ca2+]i was measured in vascular smooth muscle cells (VSMCs) using Fura-2 fluorescence. The expression of the short (OB-Ra) and long (OB-Rb) isoforms of the leptin receptor in VSMCs was evaluated by real-time reverse transcriptase-polymerase chain reaction and western-blot analysis.. Circulating leptin concentrations were increased in SHR. Serum metabolic parameters, including glucose, insulin, total cholesterol and triglyceride levels, were also elevated in SHR. Leptin did not modify the angiotensin II-induced vasoconstriction in SHR either in intact or endothelium-denuded aortic rings. In addition, leptin was not able either to diminish the angiotensin II-induced the peak rise of [Ca2+]i or to accelerate the recovery rate to basal calcium levels in VSMCs from SHR. However, OB-Ra and OB-Rb mRNA and protein expression were increased in SHR VSMCs.. The lack of effect of leptin on angiotensin II-induced contraction in the aorta of SHR is due to an impaired handling of [Ca2+]i in VSMCs. Hyperleptinemia and overexpression of OB-R in VSMCs could be compensatory mechanisms against VSMC leptin resistance in genetically hypertensive rats.

Topics: Analysis of Variance; Angiotensin II; Animals; Aorta; Biomarkers; Blotting, Western; Calcium; Disease Models, Animal; Dose-Response Relationship, Drug; Hypertension; Leptin; Male; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Protein Isoforms; Rats; Rats, Inbred SHR; Rats, Wistar; Receptors, Cell Surface; Receptors, Leptin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Vasoconstriction

The metabolic syndrome, closely associated with cardiovascular disease, is characterized by increased insulin resistance (IR). Although accelerated atherosclerosis is frequently observed in systemic lupus erythematosus (SLE), the prevalence and significance of IR remain to be elucidated. We evaluated IR in association with plasma concentrations of adipocytokines in patients with SLE.. Outpatients with SLE (n = 37) and healthy controls (n = 80) were studied. A value of the homeostasis model assessment index (HOMA-IR) > 2.0 was considered to be IR. Plasma concentrations of adiponectin and tumor necrosis factor-a (TNF-a) were measured by ELISA and leptin by radioimmunoassay.. HOMA-IR indices of the SLE patients were significantly higher than those of controls (2.3 +/- 2.3 vs 1.3 +/- 1.0, respectively; p < 0.01), although both groups exhibited a similar body mass index. The prevalence of hypertension and diabetes mellitus was significantly higher in patients with SLE compared with controls (48.6% vs 8.8% and 10.8% vs 0%). Twelve SLE patients (32%) with IR exhibited significantly higher incidence of hypertension and current proteinuria than SLE patients without IR. Plasma leptin, TNF-a, and, unexpectedly, adiponectin levels were higher in SLE patients than controls (adiponectin, 13.7 +/- 5.0 vs 9.5 +/- 3.9 microg/ml). Among the SLE patients, patients with IR showed significantly lower adiponectin levels than patients without IR (10.9 +/- 4.6 vs 15.4 +/- 4.4 microg/ml). Serum levels of adiponectin were significantly correlated inversely with HOMA-IR in SLE patients.. Elevated levels of adiponectin in SLE, despite inverse correlation with IR, suggest the possible involvement of adiponectin in IR and alterations in its effect on insulin sensitivity.

Topics: Adiponectin; Adult; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Leptin; Lupus Erythematosus, Systemic; Male; Metabolic Syndrome; Outpatients; Radioimmunoassay; Tumor Necrosis Factor-alpha

Hypertension frequently occurs in obese subjects. It has been reported that leptin and resistin induce endothelin-1 expression in vascular endothelial cells. Altered function of brain microvascular endothelial cells may be related to increased occurrences of stroke in hypertensive patients. In the present study, we therefore studied the effects of leptin and resistin on the expression of endothelin-1 and adrenomedullin in bovine brain microvascular endothelial cells. Northern blot analysis showed that leptin (10(-10)-10(-8) mol/l), resistin (10(-10)-10(-8) mol/l) or a combination of leptin and resistin (10(-8) mol/l for each) had no significant effects on the expression of endothelin-1 mRNA or adrenomedullin mRNA in cultured bovine brain microvascular endothelial cells. On the other hand, hypoxia induced, and tumor necrosis factor-alpha (10 ng/ml) decreased, the expression levels of endothelin-1 and adrenomedullin mRNAs, indicating that the bovine brain microvascular endothelial cells were able to respond to hypoxia and tumor necrosis factor-alpha. Consistent with the results of Northern blot analysis, immunoreactive endothelin and immunoreactive adrenomedullin concentrations in the medium were not significantly changed by the treatment with leptin, resistin, or a combination of leptin and resistin. The present study thus showed that neither leptin nor resistin affects the expression of endothelin-1 or adrenomedullin in bovine brain microvascular endothelial cells.

Topics: Adrenomedullin; Animals; Brain; Cattle; Cells, Cultured; Endothelin-1; Endothelium, Vascular; Gene Expression Regulation; Hypertension; Hypoxia; Leptin; Microcirculation; Peptides; Resistin; RNA, Messenger; Stroke; Tumor Necrosis Factor-alpha

Accumulating data indicate that metabolic syndrome is an inflammatory condition. Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with nephritis and cardiovascular disease. Evidence suggests that individuals with SLE are at risk for developing insulin resistance; however, this has not been directly examined. Using an established mouse strain with SLE (NZBWF1), we examined whether SLE is associated with increased body weight and fat deposition. Mean arterial pressure was significantly increased (140+/-4 versus 114+/-2 mm Hg; n > or = 5) in SLE mice by 36 weeks of age compared with control mice (NZW/LacJ). Body weight in SLE mice was higher at each age compared with controls by 12%, 22%, and 34% (n > 30). Visceral adipose tissue weight was increased in SLE by 44%, 74%, and 117% at 8, 20, and 36 weeks, respectively (n > or = 12). Plasma leptin was increased in SLE mice (8.6+/-1.0 versus 24.7+/-2.2 ng/mL; n = 5), and renal and adipose tissue exhibited macrophage infiltration. Fasted insulin was higher in SLE mice (0.6+/-0.1 versus 1.4+/-0.3 ng/mL; n > or = 10), but fasted glucose was not different (94+/-5 versus 80+/-9; n > or = 9). A glucose tolerance test caused a significantly greater and longer increase in blood glucose from mice with SLE compared with control mice. Food intake was not different between control and SLE mice. However, mice with SLE demonstrated lower levels of nighttime activity than controls. These data show that the NZBWF1 strain may be an important model to study the effects of obesity and insulin resistance on SLE-associated hypertension.

Topics: Animals; Disease Models, Animal; Female; Hypertension; Insulin Resistance; Leptin; Lupus Erythematosus, Systemic; Metabolic Syndrome; Mice; Mice, Inbred NZB; Obesity

Conflicting data suggest an association between leptin gene polymorphisms and essential hypertension independently of obesity. The aim of this study was to evaluate, in severely obese subjects, the role of one of these polymorphic markers in relation to the development of hypertension. The study included 325 obese patients with mean body mass index (BMI) of 46+/-6.94 kg/m2. One hundred sixty-six were hypertensive and 159 normotensive. In both groups, the presence of a tetranucleotide repeat in the 3' flanking region of the Ob gene was investigated using polymerase chain reaction (PCR). Due to the genetic variant, in the region studied it is possible to distinguish two alleles with different size distribution: Class I (shorter one) and Class II (longer one). Class I and Class II allele frequencies were not significantly different in obese patients when analyzed according to the presence or absence of hypertension. The results presented herein do not support a significant association of this Ob gene polymorphism with hypertension. These findings are in contrast with that reported in other populations. However, we cannot rule out that different ethnicity and/or phenotypic variability might mask small effects.

Topics: 3' Flanking Region; Adolescent; Adult; Aged; Aged, 80 and over; Female; Gene Frequency; Humans; Hypertension; Leptin; Male; Microsatellite Repeats; Middle Aged; Obesity, Morbid; Polymorphism, Genetic

Leptin seems to play a role in the pathogenesis of arterial hypertension by activation of the sympathetic nervous system, influencing water - electrolyte balance and vascular remodeling. It is not known whether leptin is a factor participating in the pathogenesis of primary arterial hypertension or its higher concentration in patients with arterial hypertension reflects only the presence of other factors leading to increased blood pressure. The aim of the study was to try to estimate the leptin participation in the development of the arterial hypertension, to evaluate the concentration of leptin in blood serum of patients with mild, moderate and severe arterial hypertension and to determine the relationships between the observed leptin concentration, arterial hypertension degree according to WHO criteria and body mass. The investigations were performed on 74 untreated patients aged 19-74 years (mean 47 +/- 12 years ). In this group there were 33 women aged 35-74 years (mean 51 +/- 10 years) and 41 men aged 19-73 years (mean 45 +/- 14 years). The mild arterial hypertension was observed in 24 patients, moderate hypertension in 34 patients and severe hypertension in 16. The obesity, identified when BMI was equal or higher than 30 kg/m2, was observed in 4 patients with mild hypertension, in 9 with moderate hypertension and in 6 with severe hypertension. All patients had normal renal function. The leptin concentration was determined by the radioimmunological method using the Human Leptin RIA Kit by LINCO Research, Inc. (Cat# HL-81 K). The analysis of the obtained results was performed using Statistica for Windows PL.V5.0.. The concentration of leptin in patients with mild hypertension was 3.61 +/- 2.22 ng/ml, in patients with moderate hypertension was 12.65 +/- 8.48 and in patients with severe hypertension 33.51 +/- 28.45 ng/ml. The concentration of leptin in obese patients was 24.83 +/- 26.60 and in patients without obesity was 10.57 +/- 11.99 ng/ml.. 1. In patients with moderate and severe hypertension the leptin serum concentration is significantly higher than mild hypertension, and in patients with severe hypertension the leptin serum concentration is significantly higher than in patients with moderate hypertension. 2. In patients suffering from arterial hypertension the leptin serum concentration is positively correlated with the body mass index. 3. The leptin serum concentration is statistically significantly higher in women with arterial hypertension as compared to the male patients with the same disease. 4. In both male and female groups of patients the leptin serum concentration is positively correlated with the arterial hypertension degree. 5. In female patients suffering from arterial hypertension the leptin serum concentration is positively correlated with the body mass and body mass index.

Topics: Adult; Aged; Appetite; Body Mass Index; Comorbidity; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity

High blood pressure (BP) is a major determinant of cardiovascular events in obesity. The beta2- and beta3-adrenoceptor polymorphisms are associated with obesity and hypertension. In the present study, we examine the relationships of beta2- and beta3-adrenoceptor polymorphisms with further weight gain-induced BP elevation in obese subjects. Changes in BP, body weight, total body fat-mass, waist-to-hip ratio, plasma norepinephrine (NE) and leptin levels, and beta2(Arg16Gly)- and beta3(Trp64Arg)-adrenoceptor polymorphisms were measured periodically over a 5-year period in 55 entry obese (body mass index [BMI]> or =25.0 kg/m(2)) normotensive (BP<140/90 mmHg) men. BP elevation and weight gain were defined as > or =10% increases from entry levels over 5 years in mean BP or BMI. Obese subjects with weight gain, BP elevation or weight gain-induced BP elevation had higher frequencies of the Gly16 allele of Arg16GIy and Arg64 allele of Trp64Arg. Subjects carrying the Gly16 or Arg64 alleles had significantly greater total fat-mass and waist-to-hip ratio at entry and over a 5-year period compared to the subjects who did not carry these polymorphisms. Subjects carrying the Gly16 allele had similar levels of plasma NE, higher levels of plasma leptin and a lower slope of the regression lines between plasma leptin and NE levels. Those carrying the Arg64 allele had higher plasma NE levels at entry and over a 5-year period compared to the subjects without the Arg64 allele, but plasma leptin levels and slopes were similar. The findings demonstrate that the Arg64 allele of the beta3-adrenoceptor polymorphisms relates to weight gain-induced BP elevation accompanying high plasma NE (heightened sympathetic activity) in obese men. The Gly16 allele of the beta2-adrenoceptor polymorphisms links to weight gain-induced BP elevation associated with leptin resistance. beta2- and beta3-adrenoceptor polymorphisms could predict the future BP elevation and further weight gain-induced BP elevation in originally obese subjects.

Topics: Adult; Alleles; Amino Acid Substitution; Blood Pressure; Body Mass Index; Cohort Studies; Humans; Hypertension; Leptin; Male; Norepinephrine; Obesity; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Receptors, Adrenergic, beta-3; Weight Gain

In this study, the levels of fibronectin, vitronectin, leptin, tissue plasminogen activator (t-PA), and lipid parameters were investigated in patients with coronary artery disease (CAD) and control group. The average plasma fibronectin levels in CAD patients group were significantly higher compared with the control group (p=0.006). Moreover, in patients with triple-vessel disease, plasma fibronectin levels were found to be significantly higher than those in the control group (p<0.05). Plasma vitronectin levels in patients with CAD were found to be significantly higher than those in the control group (p=0.000). In addition, in patients with double vessel disease plasma vitronectin levels were significantly higher than no vessel disease and control group, triple vessel disease was significantly higher as compared with no vessel disease, single vessel disease, and control group (p<0.05). We could not find any significant differences in t-PA values between CAD patients and control group. On the other hand, the average leptin levels in the group of patients were higher than those in the control group but there were no statistically significant differences found between them (p>0.05) because of high SD values. There was strong (+) correlation between fibronectin, vitronectin, and severity of disease [vitronectin/severity of disease, r = 0.5074 (p = 0.000), fibronectin/severity of disease, r = 0.2971 (p = 0.007)]. In conclusion, we can say that fibronectin and vitronectin have become greatly important in pathogenesis of coronary artery disease. High leptin levels may be contribute to platelet aggregation in patients with coronary artery disease. But, elevated serum levels of leptin cannot be useful diagnostic and monitoring markers in patients with coronary artery disease.

Topics: Adult; Aged; Body Mass Index; Cholesterol; Coronary Disease; Female; Fibronectins; Humans; Hypertension; Leptin; Male; Middle Aged; Smoking; Thrombosis; Tissue Plasminogen Activator; Vitronectin

The aim of this study was to evaluate the relationship of obesity, leptin, insulin resistance and C-reactive protein (CRP) with coronary heart disease (CHD) risk factors in patients with Type 2 diabetes mellitus (DM) with CHD compared with those with Type 2 DM without CHD.. Leptin, CRP (high sensitivity assay), fasting plasma insulin, glucose, HbA(1c) and full lipid profile were determined in 58 Type 2 diabetic patients with CHD and 87 Type 2 DM patients without CHD.. were compared between those with and without CHD. Univariate correlation as well as logistic regression analyses were used to relate these markers with traditional CHD risk factors.. Leptin showed significant correlations with BMI (r = 0.59; P < or = 0.0001), waist circumference (r = 0.45; P < 0.0001), CRP (r = 0.36; P < 0.0001), and fasting insulin (r = 0.53; P < 0.0001) as well as with systolic (r = 0.23; P = 0.007) and diastolic (r = 0.23; P = 0.007) blood pressure. However, when those with and without CHD were compared only age (P < 0.0001), duration of diabetes (P < 0.001) and degree of microalbuminuria (P = 0.02) were significantly higher in patients with CHD. Leptin (P = 0.49), CRP (P = 0.19) and lipid parameters were not significantly different between the two groups.. Our study confirms a relationship between leptin and CRP with CHD risk factors. The lack of significant difference when patients with and without CHD are compared may be due to the potential confounding effects of treatment with aspirin and statins.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Case-Control Studies; Diabetes Mellitus, Type 2; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Risk Factors; Sex Factors; Statistics, Nonparametric

High leptin levels are often observed in human obesity and are implicated in obesity-related hypertension. Leptin levels have been found to be higher in hypertensive obese African-American women compared to normotensive African-American women, but a direct association between leptin and blood pressure could not be obtained. Additionally, increased adiposity has been associated with higher aortic stiffness in obese African-American women, but leptin was not included in the study. The effects of leptin on cardiovascular function in African women have not yet been determined. We hypothesised that leptin is directly associated with blood pressure and decreased arterial compliance and that leptin levels are significantly higher in hypertensive overweight/obese African women compared to normotensive overweight/obese African women. A case-case control study was performed which included 98 African women. The subjects were divided into lean normotensive (lean NT), overweight/obese normotensive (OW/OB NT) and overweight/obese hypertensive (OW/OB HT). The Finometer apparatus was used to obtain a more elaborate cardiovascular profile. Serum leptin and insulin levels as well as the HOMA-IR index were determined. Various anthropometric measures were obtained. Leptin levels were elevated (P < or = 0.05) in the OW/OB NT and HT groups compared to the lean NT group, but were similar in the OW/OB NT and HT groups. After adjusting for obesity, insulin resistance, hyperinsulinaemia and age, a direct positive correlation was obtained between leptin and systolic blood pressure (SBP) (P < or = 0.05; r = 0.68) in the OW/OB HT group. Additionally, leptin also correlated negatively with arterial compliance (P< or = 0.05; r = -0.76) and positively with pulse pressure (P < or = 0.05; r = 0.71) in the OW/OB HT group. In conclusion, even though leptin levels were the same in OW/OB HT and NT African women, leptin was directly and positively associated with SBP and pulse pressure and negatively with C(W) only in OW/OB HT African women, independent of obesity, insulin-resistance, hyperinsulinaemia and age.

Topics: Adult; Biomarkers; Black People; Blood Pressure; Body Mass Index; Case-Control Studies; Compliance; Confidence Intervals; Female; Humans; Hypertension; Leptin; Obesity; Pulse; South Africa; Systole

Topics: Angiotensin II; Biomarkers; Humans; Hypertension; Leptin

Fatty liver is extremely common in insulin-resistant patients with either obesity or lipodystrophy and it has been proposed that hepatic steatosis be considered an additional feature of the metabolic syndrome. Although insulin resistance can promote fatty liver, excessive hepatic accumulation of fat can also promote insulin resistance and could contribute to the pathogenesis of the metabolic syndrome. We sought to create a new nonobese rat model with hypertension, hepatic steatosis, and the metabolic syndrome by transgenic overexpression of a sterol-regulatory element-binding protein (SREBP-1a) in the spontaneously hypertensive rat (SHR). SREBPs are transcription factors that activate the expression of multiple genes involved in the hepatic synthesis of cholesterol, triglycerides, and fatty acids. The new transgenic strain of SHR overexpressing a dominant-positive form of human SREBP-1a under control of the phosphoenolpyruvate carboxykinase (PEPCK) promoter exhibited marked hepatic steatosis with major biochemical features of the metabolic syndrome, including hyperglycemia, hyperinsulinemia, and hypertriglyceridemia. Both oxidative and nonoxidative skeletal muscle glucose metabolism were significantly impaired in the SHR transgenic strain and glucose tolerance deteriorated as the animals aged. The SHR transgenic strain also exhibited reduced body weight and reduced adipose tissue stores; however, the level of hypertension in the transgenic SHR was similar to that in the nontransgenic SHR control. The transgenic SHR overexpressing SREBP-1a represents a nonobese rat model of fatty liver, disordered glucose and lipid metabolism, and hypertension that may provide new opportunities for studying the pathogenesis and treatment of the metabolic syndrome associated with hepatic steatosis.

Topics: Adiponectin; Adipose Tissue; Aging; Animals; Animals, Genetically Modified; Blood Pressure; CCAAT-Enhancer-Binding Proteins; Disease Models, Animal; DNA-Binding Proteins; Fatty Liver; Gene Expression; Humans; Hypertension; Intercellular Signaling Peptides and Proteins; Leptin; Liver; Metabolic Syndrome; Rats; Rats, Inbred SHR; Sterol Regulatory Element Binding Protein 1; Transcription Factors; Transgenes

Recent studies suggest that adipose tissue hormone, leptin, is involved in the pathogenesis of arterial hypertension. However, the mechanism of hypertensive effect of leptin is incompletely understood. We investigated whether antioxidant treatment could prevent leptin-induced hypertension. Hyperleptinemia was induced in male Wistar rats by administration of exogenous leptin (0.25 mg/kg twice daily s.c. for 7 days) and separate groups were simultaneously treated with superoxide scavenger, tempol, or NAD(P)H oxidase inhibitor, apocynin (2 mM in the drinking water). After 7 days, systolic blood pressure was 20.6% higher in leptin-treated than in control animals. Both tempol and apocynin prevented leptin-induced increase in blood pressure. Plasma concentration and urinary excretion of 8-isoprostanes increased in leptin-treated rats by 66.9% and 67.7%, respectively. The level of lipid peroxidation products, malonyldialdehyde + 4-hydroxyalkenals (MDA+4-HNE), was 60.3% higher in the renal cortex and 48.1% higher in the renal medulla of leptin-treated animals. Aconitase activity decreased in these regions of the kidney following leptin administration by 44.8% and 45.1%, respectively. Leptin increased nitrotyrosine concentration in plasma and renal tissue. Urinary excretion of nitric oxide metabolites (NO(x)) was 57.4% lower and cyclic GMP excretion was 32.0% lower in leptin-treated than in control group. Leptin decreased absolute and fractional sodium excretion by 44.5% and 44.7%, respectively. Co-treatment with either tempol or apocynin normalized 8-isoprostanes, MDA+4-HNE, aconitase activity, nitrotyrosine, as well as urinary excretion of NO(x), cGMP and sodium in rats receiving leptin. These results indicate that oxidative stress-induced NO deficiency is involved in the pathogenesis of leptin-induced hypertension.

Topics: Acetophenones; Aconitate Hydratase; Aldehydes; Animals; Antioxidants; Blood Pressure; Body Weight; Creatine; Cyclic GMP; Cyclic N-Oxides; Drinking; Eating; Hypertension; Isoprostanes; Kidney; Leptin; Male; Malondialdehyde; Natriuresis; Nitric Oxide; Rats; Rats, Wistar; Reactive Nitrogen Species; Sodium; Spin Labels; Tyrosine

The levels of the liporegulatory hormone leptin are increased in obesity, which contributes to the metabolic syndrome; the latter is associated with elevated cardiovascular risk and morbidity. Leptin may play a role in the metabolic syndrome since correlations have been observed between serum leptin levels and several components of the metabolic syndrome. The association of leptinemia and hypertension or diabetes is inconsistent. Leptin levels are higher in females versus males and obese versus lean individuals. We investigated if correlations exist between leptin levels and several indices of the metabolic syndrome in obese and lean Moroccan subjects with (63 males, 129 females) and without (123 males, 234 females) diabetes and/or hypertension. Plasma glucose and insulin and systolic and diastolic blood pressures were higher in obese versus lean individuals. Obesity had no effect on lipid profile, plasma IGF-1, or C-peptide levels. Leptin levels were higher in females versus males and in obese versus lean individuals. The levels correlated significantly with body mass index. Serum leptin concentration did not correlate with either systolic or diastolic blood pressure, although there was a trend for higher blood pressure with increased leptin levels in females. There was no significant difference in leptin levels between NIDDM patients and healthy controls. However, in hypertensive patients, leptin levels were significantly higher in both lean males and females with diabetes as compared to those without diabetes. Similarly, the higher leptin levels paralleled elevated insulin levels in obese nondiabetic males and females, and in male and female diabetics with hypertension. Correlations were observed between leptin levels and C-peptide (an estimate of endogenous insulin secretion), but not with serum IGF-1. The calculated values of HOMA-IR, a marker of insulin resistance, were somewhat higher, parallel with elevated leptin levels, in obese male and female individuals compared to their lean counterparts. There was no relationship between leptin levels and serum lipids. There was a trend for increased serum uric acid levels with higher leptin concentrations. Thus, leptinemia is related to some components of metabolic syndrome, and in turn, it may contribute to the syndrome. This study is novel in that relationships were determined between leptin levels and various indices of metaboli syndrome in a large population of the same ethnic/regional background.

Topics: Aged; Blood Glucose; Blood Pressure; Body Mass Index; C-Peptide; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Leptin; Lipids; Male; Metabolic Syndrome; Middle Aged; Morocco; Obesity; Sex Characteristics; Uric Acid

Leptin is an adipocyte-derived hormone that plays a key role in the regulation of body weight through its actions on appetite and metabolism. Leptin also increases sympathetic nerve activity (SNA) and blood pressure. We tested the hypothesis that diet-induced obesity is associated with resistance to the metabolic actions of leptin but preservation of its renal SNA and arterial pressure effects, leading to hypertension. Mice were fed a high-fat diet for 10 weeks to induce moderate obesity. The decrease in food intake and body weight induced by intraperitoneal or intracerebroventricular leptin was significantly attenuated in the obese mice. Regional SNA responses to leptin were differentially altered in diet-induced obese mice. Renal SNA response to leptin was preserved, whereas lumbar and brown adipose tissue SNA responses were attenuated in obese mice. Radiotelemetric arterial pressure was approximately 10 mmHg higher in obese mice. Furthermore, the increase in arterial pressure in response to long-term (12 days) leptin treatment was preserved in obese mice. Thus, mice with diet-induced obesity exhibit circulating hyperleptinemia and resistance to the metabolic actions of leptin. However, there is preservation of the renal sympathetic and arterial pressure responses to leptin, which represent a potential mechanism for the adverse cardiovascular consequences of obesity.

Topics: Adipose Tissue, Brown; Animals; Blood Pressure; Dietary Fats; Disease Models, Animal; Drug Resistance; Hypertension; Injections, Intraventricular; Leptin; Male; Mice; Mice, Inbred C57BL; Obesity

The purpose of this study was to test whether the melanocortin-4 receptor (MC4R) is critical in the development of hypertension associated with obesity and its metabolic disorders. MC4R-deficient homozygous (-/-) and heterozygous (+/-) and wild-type (WT) C57BL/6J mice 17 to 19 weeks old (n=5 to 7 per group) were implanted with telemetry devices for monitoring 24-hour mean arterial pressure (MAP) and heart rate (HR). After 3-day stable control measurements on normal-salt diet (NSD; 0.4% NaCl), mice received a high-salt diet (HSD; 4% NaCl) for 7 days, followed by 3-day recovery on NSD. MC4R (-/-) mice were severely obese compared with MC4R (+/-) and WT mice (body weight 48+/-1.5 versus 31+/-0.6 and 30+/-0.5 g respectively). On NSD, MAP was similar in all groups of mice (MC4R (-/-) 110+/-3 mm Hg; MC4R (+/-) 109+/-2 mm Hg; WT 114+/-2 mm Hg), and HR in MC4R (-/-) was lower than in WT (604+/-5 versus 645+/-9 bpm; P<0.05) but not different from MC4R (+/-) (625+/-13 bpm) mice. HSD did not significantly alter MAP or HR in any of the groups. Epididymal and retroperitoneal fat weights and plasma leptin levels were several-fold greater in MC4R (-/-) compared with MC4R (+/-) and WT mice. Plasma insulin and glucose levels were also significantly greater in MC4R (-/-) than in MC4R (+/-) and WT mice. These data suggest that despite obesity, visceral adiposity, hyperleptinemia, and hyperinsulinemia, MC4R (-/-) mice are neither hypertensive nor salt sensitive, indicating that a functional MC4R may be necessary for the development of hypertension associated with obesity and its metabolic abnormalities.

Topics: Adipose Tissue; Animals; Blood Pressure; Body Size; Dose-Response Relationship, Drug; Drinking; Eating; Heart Rate; Hormones; Hyperinsulinism; Hypertension; Leptin; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Receptor, Melanocortin, Type 4; Sodium Chloride; Sodium Chloride, Dietary; Viscera; Weight Gain

High normal blood pressure (BP) seems to be related to increased cardiovascular risk in healthy normotensive subjects, whereas hyperleptinemia enhances both sympathetic tone and arterial BP. The aim of our study was to determine the human soluble leptin receptor number in healthy normotensive subjects with high normal BP and to compare these findings to those of healthy normotensive individuals with normal BP levels.. We studied 36 healthy normotensive individuals with high normal BP (19 men and 17 women, mean age 42+/-8 years, body mass index [BMI] 23+/-1.5 kg/m2) and 40 healthy normotensive individuals with normal BP (23 men and 17 women, mean age 43+/-7 years, BMI 23.2+/-1.4 kg/m2). The two groups are matched for age, sex, and BMI. The human soluble leptin receptor number and immunoreactive leptin levels were determined in the study population by enzyme-linked immunoassay and radioimmunoassay, respectively.. Mean plasma leptin levels were significantly higher, whereas mean human soluble leptin receptor numbers were lower in the group with high normal BP compared with the normotensive group (10+/-4.8 v 6+/-2.7 ng/mL, P<.001 and 18+/-7 v 27+/-9 IU/mL, P<.001, respectively).. Our findings indicate that normotensive individuals with high normal BP have statistically significantly higher plasma leptin levels and lower numbers of human soluble leptin receptors. This observation may play a important role in the pathogenesis of cardiovascular events in this special group of patients and needs further investigation.

Topics: Adult; Aging; Blood Pressure; Body Mass Index; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Receptors, Cell Surface; Receptors, Leptin; Sex Characteristics

Obesity induced by a high-fat diet was associated with increased tail-cuff blood pressure in adult rats. The mechanisms underlying obesity-related hypertension are unclear, but increased sympathetic activation most probably plays a role. Neuroendocrine alterations observed in obesity may influence both feeding patterns and blood pressure. Work from our laboratory has shown that chronic overfeeding in rats leads to changes in neuropeptide Y (NPY) and alpha-melanocyte stimulating hormone (alphaMSH) in the hypothalamus. These peptides have central effects on blood pressure, indicating that obesity-related changes in the CNS may impact on cardiovascular function. Population studies suggest that nutrition in early life can influence the subsequent risk of obesity and high blood pressure. To examine the impact of early postnatal overnutrition on blood pressure and adipose-derived mediators, we adjusted rat litters to 3 or 12 pups (overnutrition and control, respectively). Pups raised in small litters were 15% heavier at weaning, and this intervention was associated with a modest elevation of blood pressure and body weight as adults (16 weeks). Animals raised in small litters had increased 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) mRNA in white adipose tissue as adults, which may impact on cardiovascular function. Adjustment of diet after weaning, to 30% fat diet or standard chow, allowed comparison of the impact of different periods of overnourishment. Implementation of a high-fat diet at weaning overcame the effect of litter size on body weight from 10 weeks of age. Blood pressure rose progressively with high-fat feeding and was positively correlated with leptin and body weight. Chronic consumption of a high-fat diet led to marked increases in leptin and insulin and modest increases in blood pressure, and impacts on brain transmitters implicated in the regulation of both appetite and blood pressure. Overnourishment during early postnatal development led to profound changes in body weight at weaning, which tended to abate with maturation. It also led to long-term changes in some adipose-derived mediators, possibly increasing cardiovascular risk.

Topics: Adipose Tissue; Animals; Animals, Newborn; Blood Pressure; Dietary Fats; Energy Intake; Hypertension; Leptin; Litter Size; Male; Obesity; Rats; Weaning

Arterial hypertension is one of the reasons of high rate of mother and fetal mortality. The main aim of the study was to find the correlation between the leptin concentration, the BMI value and the risk of hypertension in pregnancy.. the study was conducted in High Risk Pregnancy Department of the Medical University of Lodz in 2001-2003. The study group consists of 126 pregnant women with arterial hypertension. BMI, leptin concentration and arterial blood pressure were measured. The measurement was done every 4 weeks from 20 weeks of gestation, Leptin Elisa kit was used. The leptin measurement was done spectrophotometrically.. In group of obese pregnant women we found the correlation between BMI and high blood pressure if the high BMI was observed before pregnancy. Leptin concentration and the risk of hypertension was higher in the group of obese pregnant women.. In obese pregnant women the risk of HA was high and the high value of BMI before pregnancy is the risk factor of hypertension in pregnancy.

Topics: Adult; Body Mass Index; Female; Humans; Hypertension; Leptin; Pregnancy; Pregnancy Complications, Cardiovascular

A successful weight loss program is essential treatment for obesity-related diseases, but it is well known that the majority of individuals do not succeed in weight loss maintenance. The present study evaluates hormonal mechanisms and the relationship of beta2-adrenoceptor polymorphisms involved in individuals who regain weight after initially successful weight loss.. Overweight Japanese men (n = 154) were enrolled in a 24-month weight loss program. Body mass index (BMI), total body fat mass, plasma norepinephrine (NE) and leptin levels, and beta2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu) were measured every 6 months for the 24-month period. Maintenance of weight loss was defined as significant weight loss (>or=10% reduction) from entry weight at 6 months and maintenance of the weight loss for an additional 18 months. Rebound weight gain was defined as significant weight loss at 6 months but subsequent regain of body weight during the next 18 months.. The results showed that 37 subjects maintained weight loss during 24 months, whereas 36 subjects had rebound weight gain. The BMI at entry and calorie intake and physical activity at each period were similar between the two groups. Subjects who maintained weight loss had at entry a significantly lower fat mass and plasma NE levels compared to those with rebound weight gain. Body fat mass, NE, and leptin levels at entry predicted the degree of change in body weight during the 24-month study period. Subjects with rebound weight gain had a significantly higher frequency of the Gly16 allele for the beta2-adrenoceptor polymorphism compared to subjects who had a 24-month maintenance of weight loss. Subjects carrying the Gly16 allele also had significantly higher plasma NE, leptin, and body fat mass levels and a greater waist-to-hip ratio both at entry and throughout the study.. A high initial degree of body fat mass and high plasma NE levels as determined by the Gly16 allele for the beta2-adrenoceptor polymorphisms predict those individuals who will have rebound weight gain after their initial successful weight loss.

Topics: Adult; Alleles; Blood Pressure; Body Mass Index; Eating; Exercise; Gene Frequency; Genotype; Heart Rate; Humans; Hypertension; Leptin; Linear Models; Male; Multivariate Analysis; Norepinephrine; Overweight; Polymorphism, Genetic; Receptors, Adrenergic, beta-2; Receptors, Adrenergic, beta-3; Time Factors; Weight Gain; Weight Loss

Although obesity is strongly associated with cardiovascular disease (CVD), the endogenous relationship between obesity and CVD is still not fully clear. Emerging evidence from both animal and human studies indicates that leptin may play an important role in obesity-related CVD. Besides modulating appetite and metabolism, leptin has also been shown to increase sympathetic nerve activity, stimulate generation of reactive oxygen species, upregulate endothelin-1 production and potentiate platelet aggregation. These effects of leptin may contribute to hypertension, endothelial dysfunction and atherosclerosis in obese individuals. Better understanding the mechanisms of leptin resistance should facilitate therapeutic approaches to reverse the phenomenon of selective leptin resistance. These recent discoveries could lead to novel strategies for treatment of obesity-associated CVD.

Topics: Animals; Cardiovascular Diseases; Endothelin-1; Humans; Hypertension; Leptin; Obesity; Reactive Oxygen Species

Adipose tissue represents an important source of angiotensinogen (AGT). We investigated the effect of obesity induced by a high-fat diet on the expression of mouse (mAGT) and human AGT (hAGT) genes in liver, kidney, and heart and different adipose depots in normal mice (C57BL/6J), and in transgenic mice expressing the hAGT gene under the control of its own promoter. Mice were fed a high-fat diet (45% kcal) or normal chow (10% kcal) for 10 and 20 wk. The expression of mAGT and hAGT mRNA was quantified using an RNAse protection assay. Mice on the high-fat diet exhibited increased weight, fat mass, and plasma leptin. Expression of mAGT or hAGT genes was not affected by high-fat diet in nonadipose tissues, brown adipose tissue, or subcutaneous white fat. In contrast, high-fat diet increased both mAGT and hAGT gene expression in visceral adipose depots (omental, reproductive, and perirenal fat). Thus obesity-induced by a high-fat diet is associated with a tissue-specific increased expression of both mouse and human AGT genes in intra-abdominal adipose tissue. Our findings also suggest that 1.2 kb of regulatory sequences present in the hAGT transgene are sufficient to transcriptionally respond to a high-fat diet in an adipose-specific and depot-specific manner.

Topics: Adipose Tissue; Angiotensinogen; Animals; Body Weight; Dietary Fats; Gene Expression; Hypertension; Leptin; Mice; Mice, Inbred C57BL; Mice, Transgenic; Obesity; RNA, Messenger

Topics: Animals; Blood Pressure; Endothelium, Vascular; Erythrocyte Membrane; Hypertension; Insulin; Leptin; Membrane Fluidity; Nitric Oxide; Obesity; Rats; Vascular Resistance

To evaluate the effect of massive weight loss on insulin sensitivity, soluble adhesion molecules, and markers of the insulin resistance syndrome (IRS).. Eighteen morbidly obese patients underwent gastric banding and were evaluated before and 6 and 12 months after surgery. Total insulin secretion, hepatic insulin extraction, and insulin sensitivity were analyzed by oral glucose-tolerance test model analysis. In addition, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, leptin, high-sensitivity C-reactive protein, plasminogen activating factor-1 (PAI-1), and tissue plasminogen activator were measured.. BMI dropped from 45.22 +/- 5.62 to 36.99 +/- 4.34 kg/m(2) after 6 months and 33.72 +/- 5.55 kg/m(2) after 12 months (both p < 0.0001). This intervention resulted in a significant reduction of blood pressure (p < 0.00001), triglycerides (p < 0.01), fasting blood glucose (p = 0.03), basal insulin (p < 0.001), and basal C-peptide (p = 0.008) levels. Total insulin secretion decreased (p < 0.05), whereas hepatic insulin extraction (p < 0.05) and oral glucose insulin sensitivity index (p < 0.0001) increased compared with baseline. Leptin (p < 0.0001) and E-selectin levels decreased significantly after 6 and 12 months (p = 0.05), whereas significantly lower levels of intercellular adhesion molecule-1 and PAI-1 were only seen after 6 months. Subclinical inflammation, measured by high-sensitivity C-reactive protein, was lowered to normal ranges. No changes were observed in vascular cell adhesion molecule-1 and tissue plasminogen activator levels.. Although gastric banding ameliorates several features of the IRS, including 29.05% improvement in insulin sensitivity and blood pressure and reduction of soluble adhesion molecules and PAI-1, considerable weight loss did not normalize all components of the IRS in morbidly obese patients.

Topics: Adult; Arteriosclerosis; C-Peptide; Cell Adhesion Molecules; E-Selectin; Female; Glucose Tolerance Test; Humans; Hypertension; Insulin; Insulin Resistance; Intercellular Adhesion Molecule-1; Leptin; Male; Obesity, Morbid; Plasminogen Activators; Stomach; Vascular Cell Adhesion Molecule-1; Weight Loss

Chronic hyperleptinemia induces arterial hypertension in experimental animals and may contribute to the development of hypertension in obese humans; however, the mechanism of hypertensive effect of leptin is not completely elucidated. We investigated the effect of leptin on whole-body oxidative stress, nitric oxide production, and renal sodium handling. The study was performed on male Wistar rats divided into 3 groups: 1) control, fed standard chow ad libitum, 2) leptin-treated group, receiving leptin injections (0.25 mg/kg twice daily s.c. for 7 days), 3) pair-fed group, in which food intake was adjusted to the leptin group. Leptin caused 30.5% increase in systolic blood pressure. Plasma concentration and urinary excretion of 8-isoprostanes in animals receiving leptin was 46.4% and 49.2% higher, respectively. The level of lipid peroxidation products, malonyldialdehyde + 4-hydroxyalkenals, increased by 52.5% in the renal cortex and by 48.4% in the renal medulla following leptin treatment, whereas aconitase activity decreased in these regions of the kidney by 45.3% and 39.2%, respectively. Urinary excretion of nitric oxide metabolites (NOx) was 55.0% lower, and fractional excretion of NOx was 55.8% lower in the leptin-treated group. Urinary excretion of cGMP decreased in leptin-treated rats by 26.3%. Following leptin treatment, absolute and fractional sodium excretion decreased by 35.0% and 41.2%, respectively. These results indicate that hyperleptinemia induces systemic and intrarenal oxidative stress, decreases the amount of bioactive NO possibly due to its degradation by reactive oxygen species, and causes renal sodium retention by stimulating tubular sodium reabsorption. NO deficiency and abnormal renal Na+ handling may contribute to leptin-induced hypertension.

Topics: Animals; Blood Pressure; Disease Models, Animal; Hypertension; Injections, Subcutaneous; Kidney; Leptin; Lipid Peroxidation; Male; Natriuresis; Nitric Oxide; Oxidative Stress; Rats; Rats, Wistar; Sodium

There has been an indication that leptin, the product of the human obesity gene, actively participates not only in metabolic regulation but also in the control of blood pressure. Recently, it has been proposed that abnormalities in the physical property of cell membranes may underlie the defects that are strongly linked to hypertension, stroke, and other cardiovascular diseases. We have shown previously that leptin significantly increased the membrane fluidity and improved the microviscosity of erythrocytes in humans through the nitric oxide-dependent mechanism. In the present study, we examined the effects of leptin on membrane fluidity of erythrocytes in subjects with essential hypertension by means of an electron paramagnetic resonance (EPR) and spin-labeling method. The values of the order parameter (S) and the peak height ratio (ho/h-1) obtained from the EPR spectra of erythrocytes were significantly greater in patients with essential hypertension (HT) than in age-matched normotensive subjects (NT) (S: HT 0.719 +/- 0.002, n = 16, NT 0.713 +/- 0.001, n = 29, P < .05; ho/h-1: HT 5.17 +/- 0.02, n = 16, NT 5.05 +/- 0.02, n = 29, P < .05). The finding indicated that the erythrocyte membrane fluidity was lower in patients with HT than in NT. Leptin decreased S and ho/h-1 in a dose-dependent manner in both NTs and HTs. The effect of leptin on the membrane fluidity was significantly more pronounced in HTs than in NTs (percent change in S: leptin 10(-8) g/mL, HT -3.4% +/- 0.2%, n = 16, NT -2.3% +/- 0.1%, n = 29, P < .05; leptin 10(-7) g/mL, HT -4.3% +/- 0.3%, n = 16, NT -3.3% +/- 0.1%, n = 29, P < .05). The results of the present study showed that leptin might have a crucial role in the regulation of the rheologic behavior of erythrocytes and the microcirculation in hypertension.

Topics: Biomarkers; Dose-Response Relationship, Drug; Electron Spin Resonance Spectroscopy; Erythrocytes; Female; Humans; Hypertension; Leptin; Male; Membrane Fluidity; Middle Aged; Statistics as Topic

Migration of aboriginal populations is thought to increase the risk of obesity and associated disorders. In this study, we examined body adiposity, glucose, insulin, leptin, and blood pressure in adult Quechua females living in rural villages in the Cuzco region [n = 105, age 35 +/- 10 yr (SD) years] and after migration to Lima from Peruvian Central Andes (n = 105, age 37 +/- 10 yr). The two populations are of the same origin and have similar fat composition in their diet, but they differ in degree of physical activity (high in Cuzco, low in Lima) and altitude of living (highland in Cuzco, lowland in Lima). The two groups had similar BMI (24.6 +/- 3.9 kg/m(2) in Cuzco vs. 25.1 +/- 4.7 kg/m(2) in Lima) and waist circumference (83.1 +/- 9.8 cm in Cuzco vs. 83.7 +/- 10.6 cm in Lima). Yet women in Lima had increased body fat mass (17.7 +/- 5.3 kg in Cuzco vs. 21.5 +/- 5.8 kg in Lima, p < 0.001) and higher diastolic blood pressure, glucose, insulin, and leptin (all p < 0.001). Also the HOMA assessment of insulin resistance was higher in Lima (p < 0.001). We conclude that migration of Peruvian Amerindian women from the Cuzco region to Lima is associated with increased risk for obesity and cardiovascular diseases without being associated with higher BMI and waist circumference.

Topics: Adipose Tissue; Adult; Body Composition; Body Mass Index; Emigration and Immigration; Female; Humans; Hypertension; Indians, South American; Insulin; Leptin; Middle Aged; Motor Activity; Obesity; Peru; Risk Factors; Rural Population; Urban Population; Women's Health

While pathogenesis of hypertension is not clearly deciphered yet, increase in body weight, most of the time, is associated with hypertension. There are reports indicating that leptin, product of the Ob gene mainly synthesized in adipocytes, may have role(s) in hypertension, but contribution of the gender is rather contradictive. In the present study, plasma leptin levels in patients of both genders with hypertension and normotensive controls were measured and the relationship between plasma leptin levels and BMI were evaluated in both sexes. Total of 62 patients (31 M/31 F) diagnosed with essential hypertension who were not under any antihypertensive medication were admitted into the study. The control group was composed of 56 (25 M/31 F) age-, BMI- and sex-matched healthy normotensive volunteers. Plasma leptin levels were determined by a commercial ELISA kit. Plasma leptin and leptin/BMI levels (Mean +/- SEM) of women (n:62) were significantly higher than men (n:56) (20.10 +/- 1.47 ng/ml versus 4.72 +/- 0.50 ng/ml; p < 0.0001). Plasma leptin and leptin/BMI levels of patients of both genders with hypertension were significantly higher than in normotensive subjects (p < 0.05). Leptin and leptin/BMI levels in obese hypertensives were higher than obese normotensives (p < 0.05). Obese hypertensive women had higher leptin and leptin/BMI levels than obese normotensive women (p < 0.05). In conclusion, these results support the hypothesis that a possible link exists between leptin and hypertension. Further studies are needed to clarify how increased levels of leptin affects the pathophysiology of hypertension.

Topics: Blood Glucose; Body Mass Index; Female; Humans; Hypertension; Insulin Resistance; Leptin; Male; Pregnancy

This study analyzes the relationship between risk factors related to overweight/obesity, insulin resistance, lipid tolerance, hypertension, endothelial function and genetic polymorphisms associated with: i) appetite regulation (leptin, melanocortin-3-receptor (MCR-3), dopamine receptor 2 (D2R)); ii) adipocyte differentiation and insulin sensitivity (peroxisome proliferator-activated receptor-gamma2 (PPAR-gamma2), tumor necrosis factor-alpha (TNF-alpha)); iii) thermogenesis and free fatty acid (FFA) transport/catabolism (uncoupling protein-1 (UCP1), lipoprotein lipase (LPL), beta2- and beta3-adrenergic receptor (beta2AR, beta3AR), fatty acid transport protein-1 (FATP-1) and iv) lipoproteins (apoliprotein E (apoE), apo CIII). The 122 members of 40 obese Caucasian families from southern Poland participated in the study. The genotypes were analyzed by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) or by direct sequencing. Phenotypes related to obesity (body mass index (BMI), fat/lean body mass composition, waist-to-hip ratio (WHR)), fasting lipids, glucose, leptin and insulin, as well as insulin during oral glucose tolerance test (OGTT) (4 points within 2 hours) and during oral lipid tolerance test (OLTT) (5 points within 8 hours) were assessed. The insulin sensitivity indexes: homeostasis model assessment of insulin resistance, whole body insulin sensitivity index, hepatic insulin sensitivity and early secretory response to an oral glucose load (HOMA-IR, ISI-COMP, ISI-HOMA and DELTA) were calculated. The single gene mutations such as C105 T OB and Pro115 Gln PPAR-gamma2 linked to morbid obesity were not detected in our group. A weak correlation between obesity and certain gene polymorphisms was observed. Being overweight (25 < BMI > or = 30 kg/m2) significantly correlated with worse FFA tolerance in male PPAR-gamma2 12Pro, LPL-H (G) allele carriers. Insulin resistance was found in female PPAR-gamma2 Pro12, TNF-alpha (-308A) and LPL-H (G) allele carriers. Hypertension linked to the PPAR-gamma2 Pro allele carriers was characterized by high leptin output during OLTT. We conclude that the polymorphisms we investigated were weakly correlated with obesity but significantly modified the risk factors of the metabolic syndrome.

Topics: Adult; Age Factors; Apolipoprotein C-III; Apolipoproteins C; Apolipoproteins E; Blood Pressure; Body Mass Index; Carrier Proteins; Dietary Fats; Fatty Acid-Binding Proteins; Female; Genetic Predisposition to Disease; Glucose Tolerance Test; Humans; Hypertension; Insulin; Insulin Resistance; Ion Channels; Leptin; Lipoprotein Lipase; Male; Membrane Proteins; Metabolic Syndrome; Middle Aged; Mitochondrial Proteins; Obesity; Poland; Polymorphism, Genetic; PPAR gamma; Receptor, Melanocortin, Type 3; Receptors, Adrenergic, beta; Receptors, Dopamine D2; Risk Factors; Tumor Necrosis Factor-alpha; Uncoupling Protein 1

To test whether leptin and adiponectin are risk markers for a first-ever stroke. RESEARCH DESIGN, METHODS AND SUBJECTS: A nested case-referent study identified 276 cases with first-ever stroke (234 cases with ischaemic and 42 with haemorrhagic stroke). Prior to the stroke, they had participated in population-based health surveys in northern Sweden (median time between survey and stroke was 4.9 years). Referents were matched for sex, age, date and type of health survey, and geographical region. Putative risk markers for first-ever stroke, including blood pressure (BP), diabetes, smoking, body mass index (BMI), cholesterol, leptin, and adiponectin, were analysed by conditional logistic regression analysis.. Increased BMI, high cholesterol and fasting glucose levels, diabetes mellitus and hypertension were found in future stroke patients. Whereas leptin levels were higher in male subjects (P = 0.004), adiponectin did not differ between groups. A high leptin level independently predicted stroke in men (OR = 2.46; 95% CI 1.08-5.62) but not in women. Adiponectin levels did not predict stroke. Males with high leptin levels developed stroke faster than males with low leptin levels (P = 0.0009), independently of traditional risk factors.. Leptin may be an important link to the development of cerebrovascular disease in men, whereas adiponectin does not associate with future stroke.

Topics: Adiponectin; Adult; Aged; Biomarkers; Blood Glucose; Body Mass Index; Cholesterol; Diabetes Complications; Diabetes Mellitus; Epidemiologic Methods; Female; Gender Identity; Health Surveys; Humans; Hypertension; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Myocardial Infarction; Proteins; Stroke

Topics: Adipose Tissue; Animals; Biological Factors; Blood Vessels; Humans; Hypertension; Leptin; Mesenteric Arteries; Obesity; Organ Specificity; Paracrine Communication; Potassium Channels; Rats; Rats, Sprague-Dawley; Rats, Zucker; Vasodilation

Obesity is among the main contributing factors in the etiology of essential hypertension (EHT). Leptin, the product of the ob gene, is expressed mainly in adipose tissue. We examined the relationship between two trace elements, zinc (Zn) and copper (Cu), and leptin in patients with EHT (n=35) and normotensive (NT) controls (n=50) because leptin as well as Zn and Cu were reported to be associated with the pathophysiology of EHT. Plasma leptin levels were determined with a commercial enzyme-linked immunosorbent assay (ELISA) kit. Atomic absorption spectrophotometry was utilized to determine plasma Zn and Cu levels. There was a negative correlation between leptin and Zn, and the Zn/Cu ratio (r= -0.359, p<0.05; r= -0.361, p<0.05, respectively) in pooled subjects. When subjects were divided based on the presence or absence of hypertension, there was a negative correlation between leptin and Zn (r= -0.375, p<0.05) as well as leptin and Zn/Cu ratio (r= -0.398, p<0.05) in NT subjects. Similar trends were observed when leptin/BMI (body mass index) levels were utilized. There was no significant correlations between levels of Cu and leptin or leptin/BMI. In conclusion, in addition to high leptin levels, Zn and the Zn/Cu ratio were lower in patients with EHT compared to NT controls.

Topics: Adipose Tissue; Adult; Body Mass Index; Copper; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Spectrophotometry, Atomic; Time Factors; Zinc

Recent findings have shown that leptin, the product of the obesity gene, may actively participate in the regulation of blood pressure and other cardiovascular functions through the nitric oxide (NO)-dependent mechanism.. In this study, to test the hypothesis that leptin regulation of NO metabolism is impaired in hypertension, we examined the possible relationship between circulating leptin and plasma NO metabolite level in normotensive (NT) and hypertensive (HT) men.. There were significant correlations between circulating leptin and BMI in both the NT and HT groups (NT: r = 0.64, n = 26, p < 0.01; HT: r = 0.59, n = 22, p < 0.01). The concentration of circulating leptin was similar between the NT and HT men, although the plasma NO metabolite level (nitrite and nitrate) was significantly reduced in the HT men compared with the NT men (NT: 51.0 +/- 4.9 microM, n = 26; HT: 37.1 +/- 2.5 microM, n = 22, p < 0.05). The circulating leptin was significantly correlated with the plasma NO metabolite level in the overall analysis of the NT and HT men (r = 0.35, n = 48, p < 0.05). When the analysis of the correlation for the NT and HT men was performed separately, there was a significant correlation between circulating leptin and plasma NO metabolites in the NT men (r = 0.45, n = 26, p < 0.05) but not in the HT men (r = 0.15, n = 22). The results of this study are consistent with the hypothesis that leptin-related metabolism of NO might be altered in HT men.

Topics: Body Mass Index; Humans; Hypertension; Leptin; Male; Middle Aged; Nitrates; Nitric Oxide; Nitrites

Obesity and hypertension are 2 closely associated conditions and obesity probably predisposed to hypertension. The mechanism of the association between obesity and hypertension is not clear. The aim of the present study was to clarify the relationship between blood pressure (BP), body mass index (BMI), serum angiotensinII (AGII) and serum leptin levels and to investigate the relation between serum AGII and leptin. This study also aimed to rule out if there is a difference in serum AGII and leptin levels between lean and obese hypertensive females.. We measured fasting serum AGII and leptin levels in 16 normotensive lean (LN) females, 25 obese normotensive (ON) females, 12 lean hypertensive (LH) females and 25 obese hypertensive (OH) females. All subjects had no evidence of preexisting cardiovascular disease, were non pregnant, had no previous history of ill health or smoking and were not on antihypertensive therapy. This study was performed in King Abdul-Aziz University Hospital, Jeddah, Kingdom of Saudi Arabia from January 2002 through to January 2003. In lean groups, there were a significant increase in BMI and serum AGII in hypertensive group compared to normotensive group while the serum leptin level was insignificantly higher in hypertensive group than in normotensive group. On the other hand, there was a significant increase in serum AGII, BMI and serum leptin for obese hypertensive compared to obese normotensive group. The mean arterial blood pressure (ABP) was significantly correlated to serum AGII, serum leptin and BMI in all groups. A significant correlation was found between serum AGII and serum leptin if all studied females (LN, LH, ON and OH) or obese females (ON and OH) were analyzed (P=0.000 and 0.04). However, in lean females (LN and LH) there was no relation between serum AGII and serum leptin.. When obesity is present, both serum AGII and serum leptin were strong predictor of BP, which is not the case in lean females in whom only serum AGII is a predictor of BP. Elevation of serum AGII and serum leptin levels when associated with increased BMI may contribute to the pathophysiology of obesity induced hypertension. Further study on leptin resistance in obese persons and its relation to increased ABP has to be carried out.

Topics: Adult; Angiotensin II; Biomarkers; Body Mass Index; Case-Control Studies; Female; Humans; Hypertension; Leptin; Obesity; Probability; Prognosis; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index

The adipose tissue-derived hormone leptin is among the physiologic processes involved in cardiovascular regulation. The aim of the present study was to elucidate if serum leptin may predict cardiovascular risk, particularly myocardial infarction (MI), in hypertensive men and women. In a prospective study cohort of hypertensive men and women, serum leptin was compared in 171 patients with MI and in 342 matched controls. The mean serum concentration of leptin was 25.1 +/- 20.0 ng/ml in the MI patients and 20.0 +/- 16.6 ng/ml in the controls (p = 0.007). The association between serum leptin and MI was independent of traditional risk factors. Leptin concentrations were higher in women than in men. In women, serum leptin was the most important predictor of MI. The present study indicates that serum leptin is associated with MI in a hypertensive population. Leptin concentrations may be of practical importance when estimating the risk of MI, especially in women, where leptin was found to be the most important predictor for MI.

Topics: Case-Control Studies; Cohort Studies; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Risk Factors

Tumour necrosis factor-alpha (TNF-alpha) has been suggested to play a key role in insulin resistance (IR) in obesity and may contribute to the development of type 2 diabetes mellitus. Recently, studies are focused on the effect of antihypertensive drugs on insulin sensitivity and cytokines. We undertook this study to evaluate the effect of amlodipine, a long-acting dihydropyridine calcium channel blocker treatment on TNF-alpha, homeostasis model assessment (HOMA) IR and leptin levels in obese hypertensive type 2 diabetic patients.. Amlodipine 5-10 mg for 12 wk was given to type 2 diabetic patients in the amlodipine group. Pre- and post-treatment values of laboratory parameters in the amlodipine group were compared with those of normotensive nondiabetic obese controls. At baseline blood pressures (BP) and metabolic parameters were measured in all patients and repeated after 12 wk in the amlodipine group.. Basal waist-to-hip ratio, systolic and diastolic BPs, fasting glucose, TNF-alpha and HOMAIR values of the amlodipine group were higher than the control group. No difference was detected in body mass index, fasting insulin, hemoglobin A1c and leptin values between groups. The systolic and diastolic BPs, fasting glucose, HOMA-IR and TNF-alpha values decreased significantly after the treatment. But, there was no correlation between percentage change in TNF-alpha and HOMA-IR.. Besides reducing BP, amlodipine seemed to improve IR and decrease TNF-alpha levels. In this context, these properties may provide additional benefits of antihypertensive drug regimens chosen for this population, but larger group interventions are needed.

Topics: Adolescent; Adult; Aged; Amlodipine; Calcium Channel Blockers; Diabetes Mellitus, Type 2; Female; Homeostasis; Humans; Hypertension; Insulin Resistance; Leptin; Lipids; Middle Aged; Obesity; Prospective Studies; Tumor Necrosis Factor-alpha

Obesity is a risk factor for high blood pressure (HBP). However, the mechanism has not been dilucidated yet. High concentrations of leptin (LEP) contributing to an increased blood pressure in obese patients via increase in the activity of the sympathetic nervous system. We explored the physiopathologic role of hyperleptinemia in HBP with regard to obesity.. Prospective and comparative study. Between February 2001 and December 2002, we studied 499 subjects, 255 with HBP and 244 without hypertension. The relationship between weight, LEP, insulin, and serum lipids with blood pressure was assessed.. Patients with HBP versus patients without HBP had a higher body mass index (30.4 +/- 3.9 to 25.5 +/- 1.7 kg/m2) (p < 0.01), higher serum concentrations of: creatinine (0.99 +/- 0.16 to 0.88 +/- 0.16 mg/dl), total cholesterol (219.5 +/- 50.4 to 190.6 +/- 40.0 mg/dl), cLDL (126.9 +/- 52.2 to 108.3 +/- 53.3 mg/dl), triglycerides (221.1 +/- 123.8 to 164.5 +/- 86.5 mg/dl), LEP (14.9 +/- 8.4 to 6.7 +/- 3.5 ng/ml) and insulin (24.2 +/- 6.5 to 16.8 +/- 4.7 mU/ml) (p < 0.01). In the univariate and multivariate analysis, obesity, dyslipidemia, hyperleptinemia and hyperinsulinemia were independent risk factors for HBP (p < 0.01).. We suggest that hyperleptinemia has a direct role in the physiopathologic mechanism of obesity-associated HBP, and it could be considered as an independent risk factor for HBP and cardiovascular disease.

Topics: Blood Chemical Analysis; Body Mass Index; Case-Control Studies; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Prospective Studies; Risk Factors

Blood pressure (BP) and heart rate (HR) responses to stress are significant predictors of cardiovascular morbidity and mortality. Because obesity is a major risk factor for cardiovascular disease, we examined whether diet-induced obesity alters the BP and HR responses to stress and whether these alterations are associated with augmented cardiovascular morbidity in the rat.. Adult male spontaneously hypertensive rats were fed either a normal diet or high-fat diet (HFD) for 12 weeks. At weeks 0 and 12, body weight was measured, and BP and HR were recorded by radiotelemetry throughout three consecutive day and night periods and in response to 30-minute immobilization stress. At the end of the 12-week intervention, the rats were sacrificed, and their organs and sera were collected.. With the intervention, HFD rats showed a significantly greater increase in body weight (as expected) and circulating leptin and free fatty acid levels compared with normal diet rats. In addition, they showed similar increases in BP and HR elevations during stress but significantly slower BP and HR decreases after stress. These HFD-induced delays in stress recovery were associated with BP and HR elevations during the night (behaviorally active) period and with augmentations in cardiac mass.. The results of this study indicate that, in spontaneously hypertensive rats, dietary obesity delays cardiovascular recovery from stress, and, in parallel, it promotes the development of nocturnal hypertension as well as cardiac hypertrophy. This suggests that dietary obesity may significantly potentiate the impact of daily stressful experiences on the cardiovascular system.

Topics: Animals; Cardiovascular System; Dietary Fats; Fatty Acids, Nonesterified; Glucose Tolerance Test; Hypertension; Kidney; Leptin; Lipids; Male; Myocardium; Obesity; Organ Size; Rats; Rats, Inbred SHR; Restraint, Physical; Stress, Physiological; Time Factors; Weight Gain

We evaluated associations of leptin with blood pressure, plasma lipid metabolism, and endocrine status in 140 perimenopausal Japanese women. In this study, the mean plasma leptin level is 8.6 +/- 4.8 ng/ml and the range is 1.7 to 29.6 ng/ml. There were significant correlations between plasma leptin concentration and systolic blood pressure (r +/- 0.647, p < 0.0001) and diastolic blood pressure (r = 0.242, p = 0.0043). We observed significant correlation of plasma leptin concentration and LDL-cholesterol, triglyceride concentrations. However, no significant differences were observed in the correlation of plasma leptin and LH, FSH, estradiol and cortisol concentrations. In conclusion, leptin showed a significant association with blood pressure and lipid metabolism. It is suggested that leptin may play an important role in physiological regulation of sympathetic nervous system and lipid metabolism in peri-and postmenopausal women.

Topics: Estradiol; Female; Gonadotropins, Pituitary; Humans; Hydrocortisone; Hypertension; Leptin; Lipoproteins; Menopause; Middle Aged; Perimenopause; Postmenopause; Triglycerides

Leptin, an important hormone for body weight regulation, may be involved in the pathogenesis of cardiovascular manifestations of obesity. We tested whether leptin may be an independent risk marker for stroke in a case-referent study.. Definitive acute stroke events, defined by MONICA criteria, were identified from October 1, 1995 to April 30, 1999. Referents without known cardiovascular disease were randomly selected from a population census. Patient characteristics were taken from hospital files and leptin was analyzed in stored samples. Logistic regression analysis was used to determine possible differences in leptin levels between groups.. One hundred and thirty-seven cases with ischemic stroke and 69 cases with hemorrhagic stroke were identified. In comparison with referents, male patients with stroke had significantly higher leptin levels. Both male and female stroke patients had increased blood pressure compared with the referents. In multivariate analyses, high leptin levels were associated with both ischemic (OR = 4.89; 95% CI: 1.89-12.62) and hemorrhagic (OR = 3.86; 95% CI: 1.13-13.16) stroke in men, and with ischemic stroke in women (OR = 4.10; 95% CI: 1.45-11.62). The combination of high leptin levels and increased blood pressure (systolic or diastolic) was associated with a strong positive interaction in males with hemorrhagic stroke.. Leptin may be an important link for the development of cerebrovascular disease in the insulin resistance syndrome in men.

Topics: Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Brain Ischemia; Case-Control Studies; Cerebral Hemorrhage; Diabetes Mellitus; Diastole; Female; Humans; Hypertension; Length of Stay; Leptin; Male; Middle Aged; Multivariate Analysis; Obesity; Risk Factors; Statistics as Topic; Stroke; Sweden; Systole

Adipocytes secrete several biologically active substances that are presumed to be involved in obesity-related hypertension. There are no reports that deal with the relationship between plasma adiponectin concentration and blood pressure (BP). To evaluate the role of adiponectin in essential hypertension 33 patients with essential hypertensive (EHP) (12 women, 21 men) and 33 body mass index-matched normotensive healthy subjects (NHS) (13 women, 20 men) were studied. In EHP plasma adiponectin concentration was significantly lower than in NHS (9.1 +/- 4.5 v 13.7 +/- 5.2 microg/mL, respectively). In all subjects a significant negative correlation was found between plasma adiponectin concentration and mean, systolic, and diastolic BP, suggesting that adiponectin contributes to the clinical course of essential hypertension.

Topics: Adiponectin; Adult; Aged; Blood Pressure; Female; Humans; Hypertension; Intercellular Signaling Peptides and Proteins; Leptin; Male; Middle Aged; Proteins

The role of leptin in the association between body mass, central adiposity, and blood pressure (BP) is controversial. This study evaluated the relationship between leptin and BP in relation to body mass index (BMI) and fat distribution in a large sample of untreated male adults.. The study population was made up of 457 untreated male employees of the Olivetti factory in Naples. Plasma leptin, complete anthropometry, BP, and relevant biochemical variables were measured.. Log-transformed plasma leptin levels were directly associated with BMI (r = 0.661, p < 0.001) and waist circumference (r = 0.630; p < 0.001). Leptin also correlated with systolic (r = 0.258) and diastolic (r = 0.277) BP (p < 0.001). The association between leptin and BP was maintained after accounting for age, BMI (or waist circumference), log-insulin, and serum creatinine (p < 0.01); this association was stronger than that with BMI. Logistic regression analysis showed that an increased prevalence of hypertension (BP >or= 140 and/or 90 mm Hg) was associated with high plasma leptin levels when controlling for age and waist circumference (odds ratio, 1.99; 95%CI, 1.06 to 3.72) or for age and BMI (odds ratio, 1.92; 95%CI, 1.02 to 3.61).. A graded positive relationship between plasma leptin levels and BP was observed in this sample of untreated male adults. This association was independent of age, BMI, abdominal adiposity, and fasting plasma insulin. Moreover, elevated plasma leptin concentrations were associated with greater probability of hypertension, again independently of potential confounders.

Topics: Adipose Tissue; Adult; Age Factors; Aged; Blood Pressure; Body Composition; Body Constitution; Body Mass Index; Cohort Studies; Creatinine; Humans; Hypertension; Insulin; Italy; Leptin; Logistic Models; Male; Middle Aged

Insulin resistance is involved in the pathogenesis of type 2 diabetes, hypertension, and atherosclerosis. Angiotensin (Ang) converting enzyme inhibitors and Ang II type 1 receptor antagonists improve insulin resistance in patients with essential hypertension, which suggest that tissue Ang II is involved in insulin resistance in patients with hypertension. To investigate the participation of tissue Ang II in insulin resistance associated with hypertension, we evaluated the Ang II-generating system in leukocytes and its relation to insulin resistance in patients with essential hypertension. Eighteen patients with essential hypertension participated in this study. Ang II was separated from leukocytes by reversed-phase high-performance liquid chromatography and measured by radioimmunoassay. Insulin resistance was evaluated by determining the steady-state of plasma glucose (SSPG) concentration. The Ang I- and Ang II-generating activities were evaluated in human leukocytes. Human leukocytes have Ang I- and Ang II-generating activities. The Ang II-generating activity was significantly inhibited by pepstatin A. Leukocyte Ang II level does not correlate with BP or plasma Ang II level in patients with essential hypertension. Leukocyte Ang II level strongly correlates with SSPG concentration, and significantly correlates with body mass index and plasma insulin, and with leptin levels in patients with essential hypertension. Leukocyte Ang II may be directly associated with insulin resistance.

Topics: Adult; Aged; Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Blood Glucose; Blood Pressure; Body Mass Index; Chromatography, High Pressure Liquid; Cilazapril; Female; Homeostasis; Humans; Hypertension; Insulin; Insulin Resistance; Leptin; Leukocytes; Male; Middle Aged

Five candidate genes including the lipoprotein lipase, leptin, leptin receptor, alpha-adducin and beta3 adrenergic receptor were selected to examine their possible contribution to essential hypertension (EH) in a Chinese population. On each side of the candidate gene loci, one to two highly polymorphic microsatellite markers were genotyped in 474 subjects recruited from 106 hypertension nuclear families in Shanghai. Both parametric and nonparametric linkage analyses were carried out using GENEHUNTER (version 2.0) after genotyping. Extended transmission disequilibrium testing (ETDT) was also conducted to detect preferential transmission of alleles to affected offspring. We failed to find the linkage between all these loci and EH by either parametric or nonparametric analysis, nor did we detect any significant transmission disequilibrium by ETDT. Our findings provide no support for a significant contribution of these five genes to the pathogenesis of EH among Shanghai people.

Topics: Asian People; Calmodulin-Binding Proteins; China; Female; Genetic Linkage; Genetic Markers; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Hypertension; Leptin; Lipoprotein Lipase; Male; Nuclear Family; Prevalence; Receptors, Adrenergic, beta-3; Receptors, Cell Surface; Receptors, Leptin; Risk Assessment

A link between leptin resistance, obesity, and salt sensitivity has been suggested. SHHF/Mcc-fa(cp) rats (SHHF) were used to study the effect of gene dosage of a null mutation of the leptin receptor (cp) on salt sensitivity and response to a combined endothelin A and B receptor antagonist (bosentan). Obese (cp/cp), heterozygous (+/cp), and homozygous lean (+/+) male SHHF were fed a low salt diet (0.3% NaCl) for 7 days, followed by a high salt diet (8.0% NaCl) for 7 days. There were no significant differences in systolic blood pressure between genotypes on low salt. In response to high salt, cp/cp had significantly greater systolic pressure than +/cp and +/+. On high salt diet, cp/cp showed a significant increase in 24 h urinary endothelin excretion and increased renal expression of preproendothelin mRNA. There was no effect of high salt diet on renal excretion of nitric oxide (NOx) or on gene expression of endothelial, neuronal, or cytokine-induced nitric oxide synthase isoforms (eNOS, nNOS, iNOS, respectively). Treatment with bosentan prevented the high salt-induced increment in systolic blood pressure in cp/cp. This was associated with a doubling of renal NOx excretion, but without changes in eNOS, nNOS, or iNOS expression. Endothelin receptor antagonism did not normalize systolic pressure in any of the genotypes. Our studies indicate that obesity secondary to leptin resistance (cp/cp) results in increased salt sensitivity that is mediated by endothelin in the SHHF rat.

Topics: Animals; Blood Pressure; Body Weight; Disease Models, Animal; Endothelins; Hypertension; Kidney; Leptin; Male; Obesity; Rats; Rats, Inbred SHR; Receptors, Endothelin; RNA, Messenger; Sodium Chloride, Dietary

To explore the links between tumor necrosis factor alpha (TNFalpha) and leptin adipose tissue expression and low-grade systemic inflammation and to determine the relationship between inflammation and the degree of adiposity, the presence of type 2 diabetes, and other cardiovascular risk factors.. Ninety-one women (BMI 19 to 65 kg/m(2)) were divided into tertiles of CRP. Insulin resistance was calculated using the HOMA method. Albumin, fibrinogen, C-reactive protein (CRP), interleukin-6, sTNFR1, sTNFR2, and leptin levels were measured in serum and plasma samples. TNFalpha and leptin expression were measured by reverse transcription-polymerase chain reaction in abdominal subcutaneous adipose tissue samples.. CRP was positively related to BMI and upper distribution of adiposity. TNFalpha and leptin adipose tissue expression were higher in the upper tertile of CRP. Also, peripheral levels of both soluble TNFRs and leptin were higher in patients with the greatest inflammation degree. Diabetes, dislipidemia, and hypertension were most prevalent in patients in the upper CRP tertile. Inflammatory markers of diabetic women were significantly different from those of nondiabetic women, even after adjusting for differences in body fat. BMI, type 2 diabetes, and adipose TNFalpha mRNA levels were significant predictors of serum CRP levels (r(2) = 0.28, p < 0.001).. These results are in agreement with the hypothesis that the synthesis of adipose tissue TNFalpha and leptin could induce the production of interleukin-6, CRP, and other acute-phase reactants, thus contributing to the maintenance of chronic low-grade inflammation state involved in the progression of obesity and its associated comorbidities.

Topics: Adipose Tissue; Adult; Antigens, CD; Body Composition; Body Mass Index; C-Reactive Protein; Diabetes Mellitus, Type 2; Female; Gene Expression; Humans; Hyperlipidemias; Hypertension; Inflammation; Insulin Resistance; Interleukin-6; Leptin; Leukocyte Count; Receptors, Leptin; Receptors, Tumor Necrosis Factor; Receptors, Tumor Necrosis Factor, Type I; Receptors, Tumor Necrosis Factor, Type II; RNA, Messenger; Tumor Necrosis Factor-alpha

Conjugated linoleic acid (CLA) is a mixture of positional and geometric isomers of linoleic acid found in beef, lamb, and dairy products. CLA has attracted considerable attention over the past several decades because of its potentially beneficial biological effects, including protective effects against several cancers, atherosclerosis, and obesity. Here we provide the first evidence that the 10trans,12cis-CLA isomer is able to suppress increases in blood pressure during the onset of obesity in OLETF rats. After 3 weeks of feeding with 10t,12c-CLA, systolic blood pressure was significantly lowered compared with rats fed linoleic acid or 9c,11t-CLA. Abdominal adipose tissue weight was also significantly lowered in rats fed 10t,12c-CLA, but not in those which were fed 9c,11t-CLA. In addition, we found that the relative mRNA expressions of angiotensinogen and leptin were suppressed by 10t,12c-CLA in adipose tissue. We speculate that the antihypertensive effect of 10t,12c-CLA can be attributed to the lowered secretion of hypertensive adipocytokines from abdominal adipose tissues.

Topics: Adipose Tissue; Angiotensinogen; Animals; Base Sequence; Dietary Fats, Unsaturated; Hypertension; Leptin; Linoleic Acid; Male; Obesity; Rats; Rats, Inbred OLETF; RNA, Messenger; Stereoisomerism

High-salt diet is known to induce or aggravate hypertension in animal models of hypertension and in humans. When Sprague-Dawley rats (n = 60) are fed a moderately high-fat diet (32% kcal fat, 0.8% NaCl) for 10 wk, about one-half develop obesity [obesity prone (OP)] and mild hypertension, whereas the other half [obesity resistant (OR)] maintain body weight equivalent to a low-fat control (C) and are normotensive. The aim of this study was to test the effect of high-NaCl diets (2 and 4% NaCl) on the development of hypertension and obesity, oxidative stress, and renal function. Both 2 and 4% NaCl induced an early increase in systolic blood pressure of OP but not OR or C rats. High-salt intake induced an increase in the size and reduction in number of adipocytes, concomitant to a twofold increase in circulating leptin in OP rats. Aortic superoxide generation indicated a 2.8-fold increase in the OP high-salt vs. normal-salt groups, whereas urine isoprostanes were not significantly increased. Also, hydroxynonenal protein adducts in the kidney were highly increased in OP rats on 2 and 4% NaCl, indicating oxidative stress in the renal tissue. Urine albumin was increased threefold in the OP on 2% NaCl and fourfold in the same group on 4% NaCl vs. 0.8% NaCl. Kidney histology indicated a higher degree of glomerulosclerosis in OP rats on high-salt diets. In summary, high-salt diet accelerated the development but did not increase the severity of hypertension; high salt increased oxidative stress in the vasculature and kidney and induced kidney glomerulosclerosis and microalbuminuria. Also, the OP rats on high salt displayed adipocyte hypertrophy and increased leptin production.

Topics: Adipocytes; Adipose Tissue; Animals; Aorta; Blood Pressure; Body Weight; Diet; Disease Susceptibility; Diuresis; Hypertension; Hypertrophy; Kidney; Leptin; Male; Obesity; Oxidative Stress; Rats; Rats, Sprague-Dawley; Renin; Sclerosis; Sodium Chloride, Dietary

In order to investigate the usefulness of angiotensin II type 1 receptor (AT1) antagonists (ARA) in the treatment of hypertension with insulin resistance syndrome, we studied the effects of a high dose sucrose diet and ARA on insulin sensitivity, plasma lipids, and leptin in spontaneous hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). SHR and WKY were divided into three groups and treated for 12 weeks: those fed a standard chow, those given a sucrose-rich chow or those given a sucrose-rich chow and ARA. While in SHR the weight of both subcutaneous and mesenteric adipose tissue was greater in the sucrose-rich chow fed animals than in the standard chow fed animals, ARA treatment significantly decreased the weights of both subcutaneous and mesenteric adipose tissue. ARA treatment decreased free fatty acid and triglyceride in SHR, and increased high density lipoprotein cholesterol in SHR and WKY. Homeostasis model assessment-insulin resistance (HOMA-IR) index, plasma levels of leptin, and leptin mRNA in mesenteric adipose tissue were significantly greater in the sucrose-rich chow fed animals than in the standard chow fed animals, and significantly lower in the ARA-treated sucrose-rich chow fed animals than in the sucrose-rich chow fed animals in both SHR and WKY. ARA improved insulin resistance, and reduced plasma leptin and leptin mRNA in adipose tissue. These results suggest that the improvement of insulin resistance by ARA may be attributed, at least in part, to the reduction of adipose tissue weight. It is concluded that ARA is useful in the treatment of patients with hypertension and concomitant insulin resistance syndrome.

Topics: Adipose Tissue; Angiotensin II Type 1 Receptor Blockers; Animals; Blood Glucose; Body Weight; Cholesterol; Cholesterol, LDL; Diet; Fatty Acids, Nonesterified; Homeostasis; Hypertension; Insulin Resistance; Leptin; Male; Organ Size; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sucrose; Triglycerides

Plasma leptin levels have been shown to be an independent risk factor for cardiovascular disease. Leptin has been shown to have sympathetic and vascular effects, and may increase cardiovascular risk through increased blood pressure, left ventricular hypertrophy, or atherosclerotic mechanisms. This study examines whether leptin levels, independent of body mass and insulin resistance, are a risk factor for hypertension and left ventricular hypertrophy.. A population-based, cross-sectional sample of 410 adults from rural Spain was studied. The correlations between plasma leptin levels and left ventricular mass index, sum of wall thicknesses, and blood pressure were calculated. Multiple linear regression analysis was used to adjust for other cardiovascular risk factors.. After adjusting for age, body mass index, systolic blood pressure, sex, and insulin resistance, leptin was inversely associated with left ventricular mass index (beta = -0.20, P < 0.01). Leptin was also inversely related to the sum of wall thicknesses; however, this association did not reach statistical significance (beta = -0.12, P = 0.063). Leptin was not statistically associated with blood pressure after adjusting for body mass index.. The results do not support the hypothesis that leptin increases cardiovascular risk by increasing left ventricular mass index or blood pressure. Other mechanisms, related to atherosclerosis, could explain the increased risk of cardiovascular diseases observed with high leptin levels.

Topics: Adult; Cross-Sectional Studies; Female; Humans; Hypertension; Hypertrophy, Left Ventricular; Leptin; Linear Models; Male; Middle Aged; Risk Factors; Spain

To assess the role of leptin in the pathogenesis of obesity-related hypertension and the relationship between blood pressure (BP), and body mass index (BMI), insulin resistance and leptin were examined.. 560 non-diabetic men, aged 35 - 75, selected from volunteers of health screening test during 2 000 were divided into hypertension group (n = 321, BP >or= 140/90 mm Hg without antihypertensive medication). and normal blood pressure group (n = 239). The body weight, waist hip ratio,BP, plasma glucose, serum lipids, true insulin (TI) and leptin were measured after overnight fast. Insulin sensitivity was assessed by the HOMA insulin resistance index (HOMA-R).. Fasting leptin level showed good correlation with BMI, fasting TI, HOMA-R, BP and also triglycerides (all P < 0.01). After adjustment for age, BMI and HOMA-R, serum leptin was still positively correlated to SBP (r = 0.11, P < 0.05), and was significantly higher in hypertensive subjects than in normotensive subjects (geometric mean 6.4 vs 4.7 micro g/L, P < 0.001). Logistic regression analysis demonstrated that leptin remained significantly associated with hypertension after adjustment for potentially confounding factors.. Leptin may play an important role in the pathogenesis of obesity related hypertension.

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Humans; Hypertension; Leptin; Logistic Models; Middle Aged; Obesity

Increased serum urate concentration is a frequent finding in patients with hypertension. Since hyperuricemia is associated with obesity, renal disease, hyperlipidemia, and atherosclerosis, whether or not serum urate is a cardiovascular risk factor per se has remained elusive. The subjects were 210 Turkish male and 210 female adults over 20 years of age. None had diabetes mellitus, endocrine diseases, or renal or hepatic disease, and those receiving antihypertensive drugs, systemic corticosteroids, or lipid-lowering drugs were excluded. Height, weight, blood pressure, serum glucose, lipid profiles, serum insulin, DHEA-SO4, and leptin were measured in the morning after an overnight fast. Women had significantly higher mean leptin (20.3 +/- 0.88 ng/mL vs 5.78 +/- 0.39 ng/mL, P < 0.001) and lower mean uric acid (248.03 +/- 4.76 micromol/L vs 311.6 +/- 5.35 micromol/L, P < 0.001), triglyceride (1.42 +/- 0.06 mmol/L vs 1.61 +/- 0.06 mmol/L, P < 0.001), and DHEA-SO4 (3.02 +/- 0.17 micromol/L vs 4.43 +/- 0.19 micromol/L, P < 0.001) concentrations than men, even when adjusted for BMI. On univariate correlation analysis, leptin showed the strongest association with BMI in both sexes and also correlated significantly with BMI, insulin, uric acid, glucose, total cholesterol, and triglycerides in males and BMI, insulin, uric acid, total cholesterol, apo B, and creatinine in females after adjustment for age and BMI. A statistical model containing creatinine, leptin, insulin, and triglycerides accounted for 34% of the variance in serum uric acid levels in men, whereas another consisting of creatinine, triglycerides, leptin, SBP, and insulin explained 42% of the variance in serum uric acid in women. The present study suggests that leptin could be one of the possible candidates for the missing link between obesity and hyperuricemia. Our study may also suggest that hyperuricemia is not only a metabolic end product but also a marker of a major pressor or pathogenic mechanism underlying the hypertension in obesity.

Topics: Adult; Body Mass Index; Cholesterol; Cross-Sectional Studies; Female; Humans; Hypertension; Hyperuricemia; Insulin; Leptin; Male; Obesity; Triglycerides; Uric Acid

We investigated whether the dietary lard-induced increase in blood pressure (BP) is accelerated in aged rats compared to young ones. Three-month-old (young group), 10-month-old (middle-age group), and 18-month-old (older group) F344/N male rats were used. The rats were fed either chow alone or chow in which 50% of the energy content was from substituted lard. Systolic BP (SBP) and body weights (BW) were determined weekly during each 7-week feeding period. A Steady-state plasma glucose (SSPG) method was used to determine the insulin sensitivity. Bilateral testicular fat mass (epididymal fat; Epi-F) was removed in order to evaluate weight (Epi-FW). SBP began to increase at 2 weeks in the older lard-fed group, at 4 weeks in the middle-age lard-fed group, and at 5 weeks in the young lard-fed group after feeding was begun. There was no significant difference in the basal values of SBP among any ages-groups of the rats. After 4 weeks of lard feeding, increases in SBP, plasma insulin, leptin level, SSPG and Epi-FW/BW were observed in the older lard-fed group. In the younger rats, however, only hyperinsulinemia developed. At 7 weeks, increased BP in the younger rats was accompanied by increased plasma leptin level, SSPG and Epi-FW/BW. In summary, aging accelerates development of a dietary lard-induced increase in BP, which may be caused by the hyperleptinemia that may be the result of increased susceptibility to insulin resistance and/or visceral adiposity in older rats.

Topics: Aging; Animals; Blood Glucose; Dietary Fats; Epinephrine; Glucose; Hypertension; Insulin; Insulin Resistance; Leptin; Male; Propranolol; Rats; Rats, Inbred F344

Obesity and high fat diets are associated with an increased prevalence of diabetes, cardiovascular disease, and hypertension. However, the mechanism(s) linking obesity and high fat diet to these metabolic and cardiovascular disorders are not fully elucidated. Leptin stimulates the formation of pro-opiomelanocortin and its products. The stimulation of the central nervous system (CNS) opioids and their receptors is associated with an increase in cardiovascular dynamics. In this study we hypothesized that obesity changed the CNS opioids and their receptors that could play a role in altered cardiovascular and autonomic nervous regulation in obesity. Male Wistar rats were fed either a high fat (HF) or regular chow (control) diet. After 12 weeks, rats were anesthetized and instrumented to record mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). A blood sample was collected and plasma glucose, insulin, leptin, beta-endorphins were measured. The brains were subsequently processed for immunohistochemistry and in situ hybridization. The HF rats were larger and had a greater percentage of body fat. Leptin and insulin levels were also higher in the HF animals. Basal MAP and RSNA were significantly higher in HF rats. Additionally, immunohistochemistry and in situ hybridization demonstrated that HF rats had increased hypothalamus mu opioid receptors compared to controls. These studies suggest that HF feeding is associated with increased body fat, plasma leptin, insulin, and hypothalamic mu opioid receptors. The increased mu opioid receptors may contribute to the higher MAP and RSNA observed in HF animals.

Topics: Animals; Arteries; beta-Endorphin; Dietary Fats; Food, Formulated; Hypertension; Hypothalamus; Immunohistochemistry; Insulin; Kidney; Leptin; Male; Obesity; Opioid Peptides; Rats; Rats, Wistar; Receptors, Opioid, mu; Sympathetic Nervous System; Vasoconstriction

Topics: Animals; C-Reactive Protein; Coronary Disease; Diabetes Mellitus; Glucose Intolerance; Humans; Hypertension; Inflammation; Leptin; Lipoproteins, HDL; Matrix Metalloproteinase 9; Metabolic Syndrome; Mice; Mice, Knockout; Obesity; Oxidative Stress; Phosphatidylcholine-Sterol O-Acyltransferase; Receptors, LDL; Risk Factors; Smoking

A high-fructose diet (HFD) has been shown to elevate blood pressure (BP) and to decrease insulin sensitivity in rats. Although running exercise can attenuate these phenomena, its effect on target organ protection is not clear. We investigated whether exercise training has renal protective effects in this model. Nine-week-old spontaneously hypertensive rats were allocated to groups that received HFD or a control diet (control group) for 15 weeks. At the age of 10 weeks, fructose-fed rats were allocated to groups that were given vehicle (FRU group), temocapril, an angiotensin converting enzyme inhibitor (TEM group), exercise training (EX group; treadmill running), or temocapril plus exercise training (TEM+EX group). BP was higher in the FRU group than in the control group. Exercise training tended to decrease BP and temocapril treatment decreased BP significantly. Proteinuria was similar in the five groups. Plasma leptin concentration and epididymal fat weight were lower in the EX and TEM+EX groups than in the FRU group. In the soleus muscle of the FRU group, the composite ratio of type I fiber was decreased and that of type IIa fiber was increased compared with those in the control group. Both temocapril and exercise training restored these ratios. The glomerular sclerosis index (GSI) was higher in the FRU group than in the control group. GSI was decreased equally in the TEM, EX, and TEM+EX groups and was positively correlated with plasma leptin concentration. The results suggest that exercise training ameliorates glomerular sclerosis through mechanisms other than a reduction in BP.

Topics: Aging; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Body Composition; Body Weight; Diet; Fructose; Glomerulosclerosis, Focal Segmental; Hypertension; Kidney Glomerulus; Leptin; Male; Muscle Fibers, Skeletal; Muscle, Skeletal; Organ Size; Physical Conditioning, Animal; Proteinuria; Rats; Rats, Inbred SHR; Thiazepines

Both hypertension and obesity are speculated to stimulate inflammation process.. Evaluation of selected inflammatory markers in obese hypertensives and estimation of their relationship to selected anthropometric and biochemical parameters. 32 patients with hypertension (group I), 34 patients with obesity and hypertension (group II) and 16 healthy volunteers (control) were studied. Percentage of fat content (%FAT) was estimated. Serum concentration of tumor necrosis factor (TNF-alpha), interleukins (IL-4, IL-6, IL-10), leptin, insulin were measured. Insulin resistance ratio (IRI/G) was calculated as an insulin: glucose ratio. Higher concentrations of TNF-alpha, IL-4, IL-6, IL-10, leptin, insulin, IRI/G ratio as compared to a control were found in both investigated groups. In group II higher TNF-alpha, IL-10, leptin, insulin and IRI/G as compared to group I were observed. In group II correlations between in (TNF-alpha) and BMI, %FAT, insulin, IRI/G ratio and SBP (systolic blood pressure) were found. BMI and TNF-alpha emerged as independent predictors of SBP.. 1. Hypertension is associated with increased level of inflammatory markers. 2. Obesity can aggravate inflammation in patients with hypertension. 3. TNF-alpha should be considered as a potential player in the state of insulin resistance in obese hypertensives. 4. Both BMI and TNF-alpha emerged as independent predictors of SBP.

Topics: Anthropometry; Female; Humans; Hypertension; Insulin; Interleukins; Leptin; Male; Middle Aged; Obesity; Tumor Necrosis Factor-alpha

It has been reported that neuropeptides may play a role in the control of appetite and in the mechanism of hormone release. Neuropeptides such as beta-endorphin, neuropeptide Y (NPY), galanin and leptin may affect hormones release, on the other hand the hormonal status may modulate neuropeptide activity.. The material consisted of 90 obese women, 30 women with Anorexia Nervosa, and 30 healthy, lean women of control group. Plasma beta-endorphin, NPY, leptin, somatostatin and serum pituitary and gonadal hormones concentrations were measured with RIA methods.. We observed the highest plasma NPY levels in obese hypertensive and diabetic patients. After carbohydrate administration (OGTT) a marked increase of insulin, beta-endorphin and NPY was found. The blunted response of GH to GH-RH may be connected with increased somatostatin activity and hyperinsulinemia. The abnormal response of LH to opioid blockade may be a result of disturbed opioid and NPY activities in obese patients. However in patients with anorexia nervosa, plasma leptin and NPY concentrations were low. The disturbances in beta-endorphin release are also observed.. The neuroendocrine disturbances in obesity and in anorexia nervosa are opposite. The feedback mechanism between leptin and NPY is disturbed in both in obesity and in anorexia nervosa. An abnormal activity of neuropeptides may lead to disturbed control of appetite and hormonal dysregulation in eating disorders.

Topics: Adult; Anorexia Nervosa; Appetite; beta-Endorphin; Diabetes Mellitus; Feedback, Physiological; Female; Glucose Tolerance Test; Human Growth Hormone; Humans; Hypertension; Leptin; Luteinizing Hormone; Neuropeptide Y; Neuropeptides; Obesity; Somatostatin

Both leptin and the renin-angiotensin system (RAS) are involved in the regulation of arterial blood pressure. This study was undertaken to assess the relationship between RAS and plasma leptin concentration in hypertensive patients under conditions of normal and restricted sodium supply and upright position.. In 31 patients with essential hypertension (EHP - 14 F, 17 M, age 44I14 years, BMI 29.3I6.4 kg/m2) and 8 healthy subjects (NHS - 4 F, 4 M, age 37(17 years, BMI 25.3I6.6 kg/m2) plasma leptin concentration, plasma renin activity (PRA), and 24-hour urinary sodium excretion (UNa) were evaluated twice: first on a diet containing 100-120 mmol sodium per day and after 8 hours overnight bed rest, and a second time after 3 days of dietary sodium restriction (10-20 mmol daily) and 3 hours in upright position.. Dietary sodium restriction and upright position was followed by a significant increase in PRA and decrease of UNa. By contrast, plasma leptin concentration showed a moderate decrease both in EHP and NHS. No significant correlation was found between PRA and plasma leptin concentrations in either of the groups examined.. From the results obtained in this study we may conclude that dietary sodium restriction and upright position exerts only a moderate effect on plasma leptin concentration, in contrast to PRA, in both hypertensive and normotensive subjects.

Topics: Adult; Body Mass Index; Diet, Sodium-Restricted; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Posture; Renin; Renin-Angiotensin System; Sodium; Sodium, Dietary

Recently a growing amount of interest has been focused on new risk factors for cardiovascular disease, such as insulin, leptin, homocysteine, and urinary albumin excretion (UAE). Furthermore, the absence of a nocturnal blood pressure (BP) decrease is emerging as an index for future target organ damage. In the present study we aimed to determine the relationship between these risk factors and circadian BP variations in essential hypertensive subjects. One hundred six patients, aged 54+/-7 years, with stage I-II untreated hypertension were classified as dippers and nondippers according to the diurnal variation of >10% between mean daytime and nighttime systolic BP (SBP) and diastolic BP (DBP) in 24-h noninvasive ambulatory BP monitoring. Venous blood samples were drawn for determination of insulin, leptin, and homocysteine plasma levels, whereas UAE was evaluated in three consecutive 24-h urine samples. Nondippers compared to dippers had significantly greater hemodynamic load and higher UAE (by 17 mg/24 h, P < .05). The two groups did not differ regarding serum insulin, plasma leptin, and homocysteine levels. In the entire population, leptin was positively correlated with age, body mass index, 24-h DBP, fasting serum insulin, and plasma homocysteine levels, whereas homocysteine levels were significantly related to 24-h SBP and DBP values. Multiple linear regression analyses revealed that only UAE was significantly related with nocturnal SBP and DBP decrease (P < .05 for both). These findings suggest that the increased UAE observed in nondipper hypertensive subjects possibly represents a useful indicator-for future target organ damage.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Cholesterol; Circadian Rhythm; Female; Homocysteine; Humans; Hypertension; Insulin; Leptin; Male; Middle Aged; Risk Factors

The effects of L-carnosine (beta-alanyl-L-histidine) on the neural activity of the renal sympathetic nerve and on DOCA-salt hypertension in rats were examined. Intravenous injection of 1 microg L-carnosine inhibited renal sympathetic nerve activity in urethane-anesthetized animals, and a diet containing 0.0001% or 0.001% L-carnosine decreased blood pressure elevation in DOCA-salt hypertensive rats. Since L-carnosine is mainly synthesized in the skeletal muscles of mammals, it is not unreasonable to postulate that L-carnosine is an endogenous factor controlling the blood pressure in a manner possibly antagonistic to the obesity-associated hypertensive effect of leptin.

Topics: Animals; Blood Pressure; Carnosine; Desoxycorticosterone; Dose-Response Relationship, Drug; Hypertension; Kidney; Leptin; Male; Rats; Rats, Sprague-Dawley; Sodium Chloride, Dietary; Sympathetic Nervous System; Time Factors

Transforming growth factor-beta1 (TGF-beta1) has been demonstrated to be overexpressed in hypertension. Leptin, an adipocyte product, has been shown to play a role in obesity-related hypertension and in vitro studies demonstrated a biologic interaction between leptin and TGF-beta1. Thus, we evaluate a possible in vivo association between TGF-beta1, body mass index (BMI), and leptin circulating levels in hypertensive subjects.. Blood samples for fasting leptin and TGF-beta1, were evaluated in 29 overweight, 46 obese, and 29 nonobese hypertensive patients before and after a 12-week calorie-restricted diet. Monocyte cultures were used for in vitro experiments.. Transforming growth factor-beta1 was significantly elevated in hypertensive obese patients (n = 46) as compared with TGF-beta1 levels of hypertensive patients with normal BMI (n = 29) (8. 9 +/- 3 ng/mL v 4.4 +/- 2; P < .001). The circulating levels of TGF-beta1 were associated with BMI and leptin levels in an univariate analysis (r = 0.59, P < .0001; r = 0.62, P < .0001, respectively) and these associations were still present after stepwise multivariate analysis. Weight loss of 10% produced a parallel decrease in TGF-beta1 (from 8.9 +/- 3 ng/mL to 5.3 +/- 2.8 ng/mL; P < .01) and leptin levels (from 30 +/- 24 ng/mL to 17 +/- 14; P < .05). In vitro experiments showed that leptin is able to induce a dose-dependent increase in TGF-beta1 production and mRNA expression in human monocyte cultures.. Our data indicate that TGF-beta1 levels are positively associated with BMI and leptin levels in hypertensive patients and suggest that adipose tissue may be an important determinant of TGF-beta1 levels possibly by a leptin-dependent pathway.

Topics: Adult; Blood Pressure; Body Mass Index; Female; Gene Expression; Humans; Hypertension; In Vitro Techniques; Leptin; Male; Middle Aged; Obesity; Regression Analysis; RNA, Messenger; Transforming Growth Factor beta; Weight Loss

1. In the present study we investigated the difference in the distribution of selected cardiovascular disease risk factors among three middle-aged Tanzanian populations with different lifestyles. 2. The prevalence of hypertension and overweight was higher in urban areas than in rural areas. Plasma leptin concentration was also highest in urban areas. Based on these results, we speculated that overweight in the urban population may be partly due to adiposity. 3. Resting energy expenditure was lower in urban areas than in other areas for both genders. These findings suggest that the high prevalence of overweight in the urban population may be partly due to low physical activity levels.

Topics: Analysis of Variance; Energy Metabolism; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Prevalence; Rural Health; Tanzania; Urban Health

To detect successsively serum leptin levels in normal, pregnancy-induced hypertension (PIH) pregnant women.. Levels of serum leptin were measured in the 16-20, 24-28, 32-36 weeks of gestation, at the delivery time in 50 healthy, 14 PIH pregnant women and their newborns and in 40 healthy non-pregnant women by Immuno-radioassay method. Serum leptin levels were correlated with body weight, body mass index (BMI), blood pressure and placental weight.. (1) The serum leptin levels were increased gradually during the normal (14.1 +/- 2.2)-(25.4 +/- 2.7) micro g/L and the PIH pregnancy [(13.4 +/- 3.0)-(21.4 +/- 3.7)] micro g/L, especially in the PIH women. It was found that leptin concentrations rose markedly from 28 to 36 weeks of gestation, but increased slightly before the 28 weeks of gestation and after the 36 weeks of gestation in normals, and in contrast to the normal pregnancy, consistently higher until to the delivery time in the PIH. (2) The positive correlations were significant between the levels of serum leptin with their body weight and BMI in the normal pregnant and non-pregnant women (r = 0.478-0.639, P < 0.05 or P < 0.01), but not significant in the PIH pregnant (r = 0.035-0.379, P > 0.05). (3) The positive correlations were significant between the serum leptin concentrations and the systolic blood pressure, diastolic blood pressure and mean artery pressure in the PIH women after 20 weeks of gestation (r = 0.639-0.852, P < 0.05), but not significant in the normal pregnant, the PIH before 20 weeks of gestation and the non-pregnant women (r = 0.113-0.498, P > 0.05). (4) Before the delivery time, the positive correlation between the serum leptin concentrations of the pregnant women and that of the newborns was not significant, and also not significant between the puerperas' serum leptin levels and the placental weight in the normal pregnant (r = 0.132, 0.097, P > 0.05). But it was interesting that significant positive correlation was found between the puerperas' serum leptin concentrations and the cord serum leptin levels (r = 0.792, P < 0.01) and significant negative correlation was detected between the puerperas' serum leptin levels and the placental weight in the PIH women (r = -0.819, P < 0.01). (5) The leptin levels of cord blood were positively correlated with the body weight and BMI of newborns in both of the normal and PIH pregnancy (r = 0.520-0.655, P < 0.05 or P < 0.01).. The characteristic change of serum leptin levels and correlations between the serum leptin concentrations and the related pregnant signs was different in normal and PIH pregnancy.

Topics: Blood Pressure; Body Mass Index; Body Weight; Female; Humans; Hypertension; Leptin; Pregnancy; Pregnancy Complications, Cardiovascular; Time Factors

Topics: Chromogranin A; Chromogranins; Family Health; Humans; Hypertension; Leptin; Likelihood Functions; Peptide Fragments; Radioimmunoassay; Risk Factors

Leptin may be a link in the relationship of obesity with hypertension. We evaluated associations of leptin with blood pressure (BP) in 54 normotensive and 114 hypertensive African American individuals. Plasma leptin was higher (P <.03) in hypertensive women than in normotensive women, although body mass index did not differ (30.5 +/- 0.5 v 30.2 +/- 0.8 kg/m(2)). After adjusting for obesity and insulin resistance, there were no significant relationships between leptin and BP; however, leptin independently predicted 28% of the variability of heart rate in hypertensive men (P <.01) and 18% of the variability of lithium clearance in hypertensive women (P <.01). Thus, in these obese hypertensive African American women, there is no direct or independent association of leptin with BP. However, leptin may contribute to hypertension in these women by increasing renal tubular sodium reabsorption.

Topics: Adult; Black People; Body Mass Index; Female; Humans; Hypertension; Insulin; Leptin; Male; Obesity; Sex Factors

The aim of this study was to evaluate the effects of moderate-intensity regular exercise and/or an angiotensin converting enzyme (ACE) inhibition on tumor necrosis factor-alpha (TNF-alpha) and glucose and lipid metabolism parameters. Spontaneously hypertensive rats (SHRs) were fed a fructose-rich diet during 16 weeks of either exercise training (Ex group: 20 m/min, 0% grade, 60 min/day, 5 days/week), administration of an ACE inhibitor (TM group: temocapril, 10 mg/kg/day), or a combination of both (TM+Ex group). The systolic blood pressure was reduced exclusively in the TM and TM+Ex group. Epididymal fat pads (EPI) weighed less in the TM+Ex group than in the single-treatment (TM) group. The serum leptin level was significantly and directly correlated with the EPI weight (p < 0.001). The TNF-alpha content per gram of EPI was the highest in the TM+Ex group. In addition, the EPI TNF-alpha level was negatively correlated with both the EPI weight and the serum leptin level (p < 0.001, respectively). In contrast, the TNF-alpha level of skeletal muscles was identical among the groups. The extensor digitorum longus had a significantly higher abundance of TNF-alpha protein than the soleus muscle. These data indicate that the local TNF-alpha expression is tissue-specific, and that upregulation of TNF-alpha in EPI by exercise training and/or ACE inhibition may have contributed to the reduction in fat cell volume via the induction of apoptosis and/or the regulation of metabolic homeostasis.

Topics: Adipose Tissue; Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Diet; Epididymis; Fructose; Hindlimb; Hypertension; Leptin; Male; Motor Activity; Muscle, Skeletal; Myocardium; Organ Size; Rats; Rats, Inbred SHR; Systole; Thiazepines; Tumor Necrosis Factor-alpha; Up-Regulation

The relationship among body fat distribution, blood pressure, serum leptin levels, and insulin resistance was investigated in hypertensive obese women with central distribution of fat.. We studied 74 hypertensive women (age, 49.8 +/- 7.5 years; body mass index, 39.1 +/- 5.5 kg/m(2); waist-to-hip ratio, 0.96 +/- 0.08). All patients were submitted to 24-hour blood pressure ambulatory monitoring (24h-ABPM). Abdominal ultrasonography was used to estimate the amount of visceral fat (VF). Fasting blood samples were obtained for serum leptin and insulin determinations. Insulin resistance was estimated by homeostasis model assessment insulin resistance index (HOMA-r index).. Sixty-four percent of the women were postmenopausal, and all patients showed central distribution of fat (waist-to-hip ratio > 0.85). The VF correlated with systolic 24h-ABPM values (r = 0.28, p = 0.01) and with HOMA-r index (r = 0.27; p = 0.01). VF measurement (7.5 +/- 2.3 vs. 5.9 +/- 2.2 cm, p < 0.001) and the systolic 24h-ABPM (133 +/- 14.5 vs. 126 +/- 9.8 mm Hg, p = 0.04), but not HOMA-r index, were significantly higher in the postmenopausal group (n = 48) than in the premenopausal group (n = 26). No correlations were observed between blood pressure levels and HOMA-r index, leptin, or insulin levels. In the multiple regression analysis, visceral fat, but not age, body fat mass, or HOMA-r index, correlated with the 24h-ABPM (p = 0.003).. In centrally obese hypertensive women, the accumulation of VF, more often after menopause, is associated with higher levels of blood pressure and insulin resistance. The mechanism through which VF contributes to higher blood pressure levels seems to be independent of leptin or insulin levels.

Topics: Adipose Tissue; Adult; Blood Pressure; Body Composition; Body Constitution; Body Mass Index; Cholesterol, HDL; Cholesterol, LDL; Diabetes Mellitus; Fasting; Female; Glucose Tolerance Test; Homeostasis; Humans; Hypertension; Hypertriglyceridemia; Insulin; Insulin Resistance; Leptin; Middle Aged; Obesity; Postmenopause; Regression Analysis; Viscera

Several neurohormonal systems have been suggested to stimulate myocardial cell growth, and thus take part in the development of left ventricular (LV) hypertrophy. We studied associations between LV mass and markers of the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system, glucose homeostasis and leptin.. A total of 115 hypertensive patients with LV hypertrophy and two age- and gender-matched control groups consisting of 38 hypertensive patients without LV hypertrophy and 38 normotensive subjects were included. We examined determinants of the RAAS, plasma levels and 24-h urinary excretions of noradrenaline and adrenaline, plasma proinsulin, insulin, glucose, leptin and LV mass by echocardiography.. Plasma renin activity (PRA) and serum aldosterone were higher (both P < 0.001) in the LV hypertrophy group than in patients without LV hypertrophy and normotensive subjects (1.0 +/- 0.8, 0.2 +/- 0.2 and 0.2 +/- 0.2 ng mL(-1) h(-1), and 327 +/- 126, 269 +/- 146 and 221 +/- 80 pmol L(-1), respectively). PRA and aldosterone both related (P < 0.001) to LV mass index (r = 0.44 and 0.27, respectively). Catecholamine levels and excretions were similar in all three groups and did not relate to LV mass index. Proinsulin, insulin and leptin levels were all elevated in the hypertensive patients (P < 0.01), but proinsulin, insulin, insulin sensitivity (by the homeostasis model assessment) and leptin did not relate to LV geometry, when indexed for body size.. Plasma renin activity and serum aldosterone levels are elevated in hypertensive LV hypertrophy and relate to LV mass index. In addition to blood pressure, activation of the RAAS may be an important nonhaemodynamic mechanism in the control of LV hypertrophy.

Topics: Adult; Aged; Blood Glucose; Blood Pressure; Catecholamines; Echocardiography; Female; Heart Rate; Homeostasis; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin; Leptin; Male; Middle Aged; Renin-Angiotensin System; Sympathetic Nervous System

Leptin regulates cardiovascular function. Leptin levels are elevated in obesity and hypertension and may play a role in cardiovascular dysfunctions in these comorbidities. This study was designed to determine the influence of hypertension on the cardiac contractile response of leptin. Mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix system in ventricular myocytes from spontaneously hypertensive (SHR) and age-matched Wistar Kyoto (WKY) rats. The contractile properties included peak shortening (PS), duration and maximal velocity of shortening/relengthening (TPS/TR(90), +/-dL/dt), and fura-fluorescence intensity change (DeltaFFI). NO and nitric oxide synthase (NOS) activity were assessed by the Griess and the (3)H-arginine/citrulline conversion assays, respectively. The leptin receptor (Ob-R) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway were evaluated by Western blot analysis. SHR animals displayed significantly elevated blood pressure and plasma leptin levels. Leptin elicited a concentration-dependent inhibition of PS and DeltaFFI in WKY, but not in SHR myocytes. Leptin did not affect TPS, TR(90), or +/- dL/dt. The difference in leptin-induced contractile response between the WKY and the SHR groups was abolished by the NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), but not by elevated extracellular Ca(2+). Either the JAK2 inhibitor AG-490 or the mitogen-activated protein (MAP) kinase inhibitor SB203580 abrogated the leptin-induced response in the WKY myocytes, whereas AG-490 unmasked a negative response in PS in the SHR myocytes. SHR myocytes displayed similar Ob-R protein abundance and basal NO levels, a blunted leptin-induced increase in NOS activity as well as enhanced basal STAT3 levels compared with the WKY group. These data indicate that the leptin-induced cardiac contractile response is abolished by spontaneous hypertension, possibly because of mechanisms involving altered JAK/STAT, MAP kinase signaling, and NO response.

Topics: Animals; Blood Pressure; Calcium; Carrier Proteins; Cell Size; DNA-Binding Proteins; Enzyme Inhibitors; Heart Ventricles; Hypertension; Imidazoles; Janus Kinase 2; Leptin; Mitogen-Activated Protein Kinase Kinases; Myocardial Contraction; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Phosphorylation; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Pyridines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Cell Surface; Receptors, Leptin; Signal Transduction; STAT3 Transcription Factor; Trans-Activators; Tyrphostins; Ventricular Dysfunction, Left

Leptin is an adipocyte-derived hormone that regulates food intake and energy expenditure. Recent functional studies have suggested a direct effect of leptin on blood pressure. In this study we examined the genetic association of the leptin gene polymorphism with obesity, insulin resistance, and hypertension. A highly polymorphic tetranucleotide repeat polymorphism in the 3'-flanking region of the leptin gene was examined. The alleles of the polymorphism consisted of two groups with different size distributions: a shorter one (class I) and a longer one (class II). The frequency of class I/class I genotype was much higher in hypertensive subjects than in control subjects (13.5% vs. 3.4%; P = 0.0027). No significant difference in body mass index was observed with different genotypes in either patients with hypertension or control subjects. Insulin responses to glucose and insulin sensitivity were not different among patients with different genotypes. The leptin gene polymorphism was associated with hypertension independent of obesity. These data together with recent functional data on the direct effect of leptin on blood pressure suggest that the leptin gene and its product, leptin, are an attractive target for studies on the mechanisms of hypertension and for the development of methods for the prediction, prevention, and therapy for hypertension.

Topics: Aged; Alleles; Female; Gene Frequency; Genotype; Humans; Hypertension; Insulin Resistance; Leptin; Male; Microsatellite Repeats; Middle Aged; Obesity; Polymorphism, Genetic; Reference Values

The elevation of renal sympathetic nervous activity (SNA) is a possible cause of blood pressure (BP) elevation. Although a high-fat diet (FAT) often induces BP elevation in animals, the effect of FAT on renal SNA in animals is not consistent between studies. Thus, we compared the basal levels of efferent renal SNA and BP in FAT- or high-carbohydrate diet (CHO)-fed rats. Twenty-four male Sprague-Dawley rats were fed FAT (P/F/C=20/45/35% cal) or CHO (20/5/75) from 5 weeks of age. After 20-21 weeks of feeding, a 24-h urine sample was collected to measure sodium excretion. The next day, blood (0.2 ml) was withdrawn from a femoral artery, and basal efferent renal nerve discharges and mean arterial pressure (MAP) were recorded under anesthesia. Immediately after the experiment, abdominal (epididymal, perirenal and mesenteric) adipose tissues were dissected. Total abdominal fat weight was significantly greater in the FAT group than in the CHO group. The plasma level of leptin was significantly higher in the FAT group, but blood glucose and plasma insulin levels did not differ between the two groups. MAP and renal SNA were significantly higher in the FAT group. In addition, the ratio of urinary sodium excretion to dietary sodium intake was significantly lower in the FAT group than in the CHO group. The data suggest that the increased renal SNA may contribute to BP elevation in FAT-fed rats. The present study firstly demonstrated that renal SNA was elevated with FAT-related BP elevation.

Topics: Animals; Blood Pressure; Body Weight; Dietary Carbohydrates; Dietary Fats; Heart Rate; Hypertension; Kidney; Leptin; Male; Rats; Rats, Sprague-Dawley; Sodium; Sympathetic Nervous System

Multiple factors are involved in the pathogenesis of hypertension in the obese individual. To evaluate the role of a decrease in sympathetically mediated thermogenesis and the effect of the correlation between the plasma leptin and daily urinary nitric oxide levels on obesity-related hypertension.. We evaluated three groups: 25 obese hypertensive patients (age 45.7 +/- 1.37 years, body mass index 34.2 +/- 1.35 kg/m2, systolic/diastolic blood pressure 155 +/- 2.9/105 +/- 1.3, mean arterial pressure 122 +/- 1.50 mmHg); 21 obese normotensive patients (age 39.6 +/- 1.72, BMI 31.3 +/- 0.76, SBP/DBP 124 +/- 2.1/85.4 +/- 1.8, MAP 98.2 +/- 1.80); and 17 lean normotensive subjects (age 38.1 +/- 2.16, BMI 22.1 +/- 0.28, SBP/DBP 117 +/- 1.7/76.8 +/- 1.5, MAP 90.1 +/- 1.50). We determined basal resting metabolic rates, plasma insulin (radio-immunoassay), norepinephrine (high performance liquid chromatography) in all subjects. Thereafter, 14 obese hypertensives underwent a weight reduction diet. At weeks 6 (n = 14) and 14 (n = 10) of the diet the above determinations were repeated. Plasma leptin (enzyme-linked immunosorbent assay) and UNOx (spectrophotometry) were assayed in 17 obese hypertensives and 17 obese normotensives, and in 19 obese hypertensives versus 11 obese normotensives, respectively.. Obese hypertensive patients had significantly higher basal RMR and plasma NE levels insulin levels were lower in the lean group, with no difference between the hypertensive and normotensive obese groups. At weeks 6 and 14, BMI was significantly lower, as were insulin and NE levels. RMR decreased to values of normotensive subjects. MAP normalized but remained significantly higher than in obese normotensives. Leptin blood levels and the leptin/UNOx ratio were significantly higher in the obese hypertensive compared to the obese normotensive patients. Both these parameters were strongly correlated to BMI, MAP, RMR, and plasma NE and insulin. Obese hypertensive patients excreted less urinary NO metabolites. A strong correlation was found between MAP and the leptin/UNOx ratio.. A reduction in sympathetically mediated thermogenesis, as reflected by RMR, results in normalization of obesity-related hypertension. In contrast, insulin does not seem to play a major role in the pathogenesis of hypertension associated with obesity. Increased leptin levels in conjunction with decreased NO production in the presence of enhanced sympathetic activity may contribute to blood pressure elevation in the obese.

Topics: Adult; Analysis of Variance; Basal Metabolism; Chromatography, High Pressure Liquid; Diet, Reducing; Enzyme-Linked Immunosorbent Assay; Humans; Hypertension; Insulin; Leptin; Male; Middle Aged; Nitric Oxide; Norepinephrine; Obesity; Radioimmunoassay

Obesity, type II diabetes, hypertension, and dyslipidemia are major causes of morbidity and mortality throughout the world. Though these disorders often cluster in individuals and families and are collectively known as syndrome X, the basis for this aggregation is not well understood. To further understand the pathogenesis of syndrome X, a comprehensive epidemiological study was undertaken on the Pacific Island of Kosrae, Federated States of Micronesia (FSM).. The entire adult (>20 years of age) population of Kosrae underwent a clinical evaluation that included a questionnaire that noted the participants' sex, family data including listing of biological parents, siblings, and children, smoking status, village of residence, age and health status. The medical evaluation included: anthropometric measures (weight, height, waist, hip), serum chemistries (leptin, fasting blood sugar (FBS), insulin, total cholesterol (TC), triglycerides (TG), and apolipoproteins B and A-I (apo B and apo A-I) and blood pressure (BP) measurements.. Obesity (BMI >/=35) was found in 24%, diabetes (FBS >/=126 or 2-hour oral glucose tolerance test >/=200) in 12%, hypertension (SBP >/=140 or DBP >/=90) in 17%, and dyslipidemia (TC >/=240 or TG >/=200 or apo B >/=120 or apo A-I

Topics: Adult; Apolipoprotein A-I; Apolipoproteins B; Blood Glucose; Blood Pressure; Cholesterol; Diabetes Mellitus, Type 2; Factor Analysis, Statistical; Female; Humans; Hyperlipidemias; Hypertension; Insulin; Insulin Resistance; Leptin; Male; Micronesia; Middle Aged; Obesity; Risk Factors; Triglycerides

Left ventricular (LV) hypertrophy is an important predictor of cardiovascular morbidity and mortality. Hemodynamic factors, such as 24-h blood pressure (BP) values, are responsible for left ventricular hypertrophy in hypertensives. On the other hand, some metabolic factors have also been suggested to affect LV mass and geometry. In particular, plasma leptin concentrations have been found associated to LV myocardial growth. Because chronic leptin infusion stimulates sympathetic nervous system activity and increases BP levels, the role of 24-h BP values on leptin-related changes in myocardial wall geometry cannot be ruled out. Thus, the aim of our study was to evaluate whether the relationship between plasma leptin levels and LV wall thickness is mediated by 24-h BP values in hypertensive male patients. Thirty-six newly diagnosed hypertensive patients underwent Doppler echocardiographic examination, 24-h ambulatory BP recording, and metabolic (euglycemic hyperinsulinemic glucose clamp and fasting plasma leptin levels) measurements. Left ventricular mass correlated positively only with ambulatory diastolic BP (DBP) values, whereas the indices of myocardial wall growth such as interventricular septum thickness and sum of wall thickness (ie, septal + posterior wall thickness) correlated either with 24 h, daytime, or nighttime DBP, as well as with fasting plasma glucose, fasting plasma leptin, and insulin action after adjustment for age, body mass index (BMI), and waist/hip ratio (WHR). In contrast, plasma leptin concentration did not correlate with clinical and ambulatory BP values. A multiple linear regression analysis allowed to investigate the independent role of main anthropometric and cardiovascular covariates on the sum of wall thickness variability. A model that includes age, BMI, WHR, fasting plasma leptin concentration, plasma Na+ concentration, insulin action, and nighttime DBP explained 68% of the sum of wall thickness variability. In such a model, plasma leptin concentration (P < .001), insulin action (P < .029), and nighttime DBP (P < .002) were significantly and independently associated with myocardial wall thickness. In conclusion, our study demonstrates that in hypertensive men fasting plasma leptin levels are determinant of myocardial wall thickness independently of 24-h BP values.

Topics: Adult; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Echocardiography; Humans; Hypertension; Hypertrophy, Left Ventricular; Insulin; Leptin; Male; Middle Aged; Osmolar Concentration

To investigate whether hypertensive disorders of pregnancy alter the maternal and fetal leptin levels.. Fifty primigravidas between 28 and 34 weeks of gestation were divided into three groups: group A consisted of 17 normal pregnant women with a mean gestational age of 31 weeks, group B consisted of 15 women with gestational hypertension without proteinuria with a mean gestational age of 30 weeks and group C consisted of 18 pre-eclamptic women with a mean gestational age of 31 weeks.. The pre-eclamptics had significantly higher serum leptin levels than those in normal pregnancies (p<0.001) but no difference was noted between normal and gestational hypertensive pregnancies. Pre-eclamptic women had significantly higher umbilical vein leptin levels (4.68+/-1.66ng/ml) compared to normal pregnancies (1.92+/-0.71ng/ml) and those with gestational hypertension (2.47+/-0.81ng/ml).. Pre-eclampsia is associated with an increase in maternal plasma leptin levels and fetal of leptin production increases in gestational hypertension and even more in pre-eclampsia.

Topics: Adult; Female; Fetal Blood; Humans; Hypertension; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular; Reference Values

Studies reveals that plasma leptin levels (LEP) in females are higher than those in males, and that LEP in hypertensive subjects are higher than those in BMI-matched normotensive subjects. To investigate the relationships among LEP, blood pressure (BP) and insulin sensitivity, we studied these relationships in 133 Japanese males and 263 females. LEP were positively correlated with BP, body mass index, body fat mass (FM) and homeostasis model assessment (HOMA). Regression analysis in which age and FM were adjusted showed LEP were associated with BP and HOMA. Even with adjustment by age, FM and HOMA, LEP were still positively correlated BP in males. LEP in insulin-resistant hypertensives was significantly higher than those in insulin-sensitive hypertensives, in insulin-sensitive normotensives and in insulin-resistant normotensives in males. However, in females, a significantly higher LEP was observed in insulin-resistant subjects than in insulin-sensitive subjects regardless of hypertension. These data suggest that it would be sexual difference in the relationships among hyperleptinemia, hyperinsulinemia and hypertension.

Topics: Adult; Blood Pressure; Body Mass Index; Female; Humans; Hyperinsulinism; Hypertension; Insulin; Insulin Resistance; Japan; Leptin; Male; Middle Aged; Population Surveillance; Sex Factors

This study was conducted to clarify the mechanisms involved in the sensitivity for blood pressure (BP) reduction in response to weight loss. In particular, we focused on the contributions of sympathetic nervous system activity and fasting plasma leptin and insulin levels to BP levels during weight loss in obese subjects with weight loss-sensitive and -resistant BP reduction. Sixty-one young, obese untreated hypertensive men (HT) and 52 obese normotensive men (NT) were enrolled in a weight loss program consisting of a low caloric diet and aerobic exercise over a 24-week period. At entry and at week 24, body mass index (BMI), BP, plasma norepinephrine (NE), leptin and insulin were measured. Successful weight loss and BP reduction were respectively defined as a more than a 10% reduction in BMI or mean BP from baseline at week 24. More than 60% of subjects in either group successfully achieved weight loss by this definition. The percentage of subjects who successfully achieved BP reduction was higher (64%) among those subjects who achieved weight loss than among those who did not (22%). Plasma NE level at entry in subjects who failed to achieve BP reduction despite weight loss was significantly higher than that in subjects who succeeded in BP reduction. Plasma leptin and insulin levels were similar between subjects with and without BP reduction. In addition, the absolute decrement and percent decrement in plasma NE in subjects who succeeded in BP reduction were significantly greater than those in subjects who failed to reduce their BP. Absolute and percent decrements in plasma leptin and insulin were similar in both groups. These results suggest that individuals who are resistant to weight loss-induced BP reduction have more sympathetic overactivity both at the outset of and during weight loss.

Topics: Adult; Blood Pressure; Body Mass Index; Humans; Hypertension; Insulin; Leptin; Male; Norepinephrine; Obesity; Sympathetic Nervous System; Weight Loss

Leptin concentrations are increased during late pregnancy, and leptin receptors are expressed in placental and fetal tissues, suggesting a role for leptin in placental and/or fetal growth, or both. In humans, leptin concentrations in adulthood are inversely related to body weight at birth, independent of adult adiposity, and correlate with fasting insulin. Glucocorticoids and insulin regulate leptin secretion. Excessive exposure to glucocorticoids during late fetal development in the rat causes intrauterine growth retardation (IUGR), together with hypertension and hyperinsulinaemia in adulthood. Leptin may have a role in the development of some forms of hypertension.. To determine whether IUGR induced by maternal glucocorticoid treatment during the last third of pregnancy in the rat is associated with modulation of either maternal or fetal leptin concentrations, the placental expression of leptin or the short form of the leptin receptor (ObR-S), or combinations thereof, and to evaluate whether hypertension or hyperinsulinaemia in the early-growth-retarded adult progeny of dexamethasone-treated dams is associated with altered leptin concentrations.. Dexamethasone was administered to pregnant rats from day 15 to day 21 of gestation via a chronically implanted subcutaneous osmotic minipump. Protein expression of leptin and ObR-S in the placenta at day 21 of pregnancy was measured by western blotting. Plasma leptin and insulin concentrations were determined by radioimmunoassay and ELISA respectively. Systolic hypertension was measured by tail cuff plethysmography.. Dexamethasone administration during the last third of pregnancy decreased placental mass and fetal body weight at day 21 of gestation, caused maternal hyperleptinaemia but fetal hypoleptinaemia, and suppressed placental leptin protein expression whilst up-regulating placental protein expression of ObR-S. The male and female offspring of dexamethasone-treated dams were hypertensive from 12 weeks of age. One-year-old offspring of dexamethasone-treated dams exhibited significant hyperleptinaemia compared with age-matched controls, an effect associated with hyperinsulinaemia in the male, but not female, offspring.. The rat model of maternal dexamethasone treatment is established as a paradigm of 'programmed' hypertension in man. Our data show modification of placental leptin and leptin receptor protein expression by dexamethasone treatment during the last third of pregnancy. We also show that leptin concentrations are suppressed during fetal life but increased in adulthood in this rat model of programmed hypertension. Our data do not necessarily establish a causal relationship between fetal hypoleptinaemia and impaired fetal growth during early life, or between hyperleptinaemia and hypertension in adulthood. Nevertheless, they suggest that hyperleptinaemia may be a component of the cluster of metabolic abnormalities seen in the insulin resistance syndrome in man. They also suggest that excessive fetal exposure to glucocorticoids could be a common early-life stimulus to the association between hyperinsulinaemia, hypertension and hyperleptinaemia often seen in individuals of low birthweight.

Topics: Animals; Body Weight; Carrier Proteins; Dexamethasone; Dose-Response Relationship, Drug; Eating; Embryonic and Fetal Development; Female; Fetal Growth Retardation; Fetus; Glucocorticoids; Hypertension; Insulin; Leptin; Male; Organ Size; Placenta; Pregnancy; Pregnancy, Animal; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Receptors, Cell Surface; Receptors, Leptin; Time Factors

Caloric restriction of mammals leads to decreases in blood pressure and heart rate. Although relevant clinically, the mechanisms involved, in terms of hormones and signaling pathways invoked, are currently not known. Circumstantial evidence suggests that leptin signaling may be involved with the bradycardia and hypotension associated with caloric restriction. This hypothesis was specifically tested using leptin-deficient mice (ob/ob) or leptin-receptor rats (Koletsky). Ob/ob mice were hypertensive during the light cycle relative to littermate controls (108 +/- 2 vs. 100 +/- 2 mmHg, respectively). Both ob/ob mice and wild-type mice exhibited hypotension and bradycardia on initiation of a 50% caloric restriction regime, suggesting that the loss of leptin during caloric restriction is not required to explain the cardiovascular effects. Blood pressure in Koletsky rats did not drop in response to caloric restriction during the light cycle, whereas blood pressure in littermate control rats significantly dropped. These data suggest that at least two pathways are involved with cardiovascular effects of caloric restriction: one dependent on leptin signaling and the other independent of the leptin axis.

Topics: Animals; Blood Pressure; Bradycardia; Energy Intake; Female; Gene Expression; Heart Rate; Hypertension; Hypotension; Leptin; Mice; Mice, Obese; Myosin Heavy Chains; Photoperiod; Rats; Rats, Inbred Strains; RNA, Messenger; Signal Transduction

On the basis of evidence of plasma leptin (LE) effects on cardiovascular system, we assessed possible association of LE and Doppler-derived left ventricular (LV) diastolic function in arterial hypertension.. Doppler echocardiography, blood sample for fasting plasma LE levels, and euglycemic hyperinsulinemic glucose clamp were performed on 15 healthy insulin-sensitive men and 40 newly diagnosed hypertensive men, who were divided into two groups according to insulin sensitivity degree: 15 insulin sensitive (IS) and 25 insulin resistant (IR) individuals (whole body glucose disposal >33.3 and <33.3 micromol/kg, respectively).. The IR hypertensives had significantly higher body mass index (BMI), waist/hip ratio, LE and LV mass index than the other two groups. IR hypertensives had lower LE (even after adjusting for BMI and waist/hip ratio) and among LV diastolic indexes, lower E peak velocity (P < .05) and longer isovolumic relaxation time (IVRT) (P < .001) in comparison to IR hypertensives. IR hypertensives had the lowest E/A ratio (0.88 +/- 0.2) compared to IS patients (1.03 +/- 0.1 P < .05) and controls (1.31 +/- 10.2 P < .001). By multiple linear regression analyses performed both in the overall population and hypertensives, LV mass index and LE were independently associated to IVRT (R2 = 0.41 in overall population, R2 = 0.42 in hypertensives, both P < .0001), whereas age, heart rate, diastolic and systolic blood pressure (BP), BMI, waist/hip ratio, and insulin action were not significant.. Our study underscores an independent association of increased plasma LE and lengthening of isovolumic relaxation in uncomplicated hypertension. Further studies will need to understand the conditions underlying both these phenomena.

Topics: Adult; Diastole; Echocardiography, Doppler; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Ventricular Function, Left

This study was conducted to evaluate the relative contributions of existing obesity and a family history of obesity (FHOB) to blood pressure (BP) level, sympathetic activity, plasma leptin and insulin levels in young men without a family history of hypertension. The study was of "four-corner" design according to body mass index (BMI). A positive FHOB (FHOB+) was defined as both parents being obese (BMI >26.0 kg/m2), and a negative FHOB (FHOB-) was defined as both parents being lean (BMI <22.0 kg/ m2). The cutoff limits of BP for the subjects and their parents enrolled in present study was defined as a supine reading of <140/90 mmHg. In 12 lean young subjects with FHOB-, 9 obese young subjects with FHOB-, 8 lean young subjects with FHOB+ and 16 obese young subjects with FHOB+, BMI, BP, plasma norepinephrine (NE), insulin and leptin were measured. All subjects were men and non-diabetic. Obese subjects, irrespective of FHOB, had higher levels of BMI, BP, plasma NE, leptin and insulin compared to lean subjects. In subjects with FHOB+, regardless of their current degree of adiposity, there was a higher level of BP and plasma NE than in subjects with FHOB-. In lean subjects, FHOB+ was associated with a higher plasma NE level and BP, but similar levels of plasma leptin and insulin were found when compared with FHOB- subjects. These results suggest that existing obesity and a positive family history of obesity appear to have an association with sympathetic overactivity and BP elevation.

Topics: Adult; Blood Pressure; Body Mass Index; Case-Control Studies; Family Health; Humans; Hypertension; Insulin; Leptin; Male; Norepinephrine; Obesity; Parents; Sympathetic Nervous System

Topics: Humans; Hyperinsulinism; Hypertension; Insulin Resistance; Leptin; Obesity; Syndrome

We investigated whether hypertriglyceridemia and hyperleptinemia are involved in the development of increases in blood pressure induced by dietary lard. Rats received either chow alone or chow in which 50% of the energy content was from substituted lard. Each group was divided into two groups according to whether the diet included bezafibrate or not. In another series of experiments, rats were fed either chow alone or chow in which 50% of the energy content was from substituted lard, safflower oil, or sucrose. Systolic blood pressure (SBP) was measured every week during each 7-week feeding period. A steady-state plasma glucose method was used to determine insulin sensitivity after lard substitution with or without bezafibrate. After the 7-week feeding period, the plasma levels of glucose, immunoreactive insulin, triglyceride and leptin were measured. In rats fed with a high lard diet, SBP, plasma levels of immunoreactive insulin, triglyceride, leptin and steady-state plasma glucose concentrations significantly increased, compared with levels of these substances in controls. Bezafibrate treatment completely reversed these effects. In rats fed with a high safflower oil or a high sucrose diet, no significant change was seen in SBP and plasma immunoreactive insulin levels. However, the plasma triglyceride levels were increased by dietary lard or sucrose. Moreover, the plasma leptin level was also increased by dietary lard and safflower oil. Neither dietary hypertriglyceridemia nor hyperleptinemia were involved in the development of increases in blood pressure induced by dietary lard.

Topics: Adipose Tissue; Animals; Bezafibrate; Blood Glucose; Blood Pressure; Cholesterol; Diet; Dietary Fats; Hypertension; Hypertriglyceridemia; Hypolipidemic Agents; Insulin; Leptin; Male; Rats; Rats, Wistar; Safflower Oil

Topics: Humans; Hypertension; Leptin

Previous studies have demonstrated that elevated plasma leptin concentrations are associated with essential hypertension. It has also recently been shown that leptin plays a promoting role in angiogenesis, and the vascular endothelium expresses the long form of leptin receptor. Those data led us to hypothesize that leptin might contribute to end-organ damage in hypertension. Thus, in the present study we evaluated the relationship between plasma leptin concentrations and hypertensive retinopathy (HR). One hundred and eleven patients newly diagnosed with essential hypertension [EHT; mean age, 43.5 +/-10.7 yr; body mass index (BMI), 28.1 +/- 4.4 kg/m2; male/female ratio, 71/40] and 79 healthy normotensive control subjects (NT; mean age, 43.6 +/- 9.2 yr; BMI, 28.2 +/- 3.3 kg/m2; male/female ratio, 50/29) were enrolled in the study. For the assessment of retinopathy according to the Keith-Wagener classification, direct and indirect ophthalmoscopy were performed in all subjects after dilatation of the pupils. Plasma leptin levels were significantly higher in EHT (11.8 +/- 11.1 ng/mL) than in NT (7.2 +/- 5.1 ng/mL) (P = 0.003). Plasma leptin concentrations were strongly correlated with BMI in both EHT (r = 0.45; P = 0.001) and NT (r = 0.38; P = 0.001) groups. Plasma leptin in patients with grade 2 HR (24.8 +/- 15.8 ng/mL; n = 22) was significantly higher than that in patients with grade 1 HR (16.1 +/- 4.9 ng/mL; n = 29; P = 0.001), grade 0 HR (5.1 +/- 3.1 ng/mL; n = 60; P = 0.001), and NT (P = 0.001). Plasma leptin in patients with grade 1 HR was also significantly higher than that in patients without retinopathy (P = 0.001) or in NT (P = 0.001). The estimated threshold of plasma leptin concentration for HR was 10.2 ng/mL. This critical leptin level served largely to separate patients with retinopathy from those without retinopathy. In summary, our results show that plasma leptin concentrations increase progressively with higher grades of hypertensive retinopathy even after correction for BMI, suggesting that a critical leptin level is needed for the development of retinopathy. Elevated concentrations of plasma leptin might be secondary to release of leptin by the vascular endothelium damaged by high blood pressure, as an epiphenomenon. However, a pathogenic role for leptin in hypertensive retinopathy cannot be excluded.

Topics: Adult; Body Mass Index; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Ophthalmoscopy; Reference Values; Retinal Diseases

To explore the pathophysiological role of leptin in obesity-related hypertension, we examined cardiovascular phenotypes of transgenic skinny mice whose elevated plasma leptin concentrations are comparable to those seen in obese subjects. We also studied genetically obese KKA(y) mice with hyperleptinemia, in which hypothalamic melanocortin system is antagonized by ectopic expression of the agouti protein. Systolic blood pressure (BP) and urinary catecholamine excretion are elevated in transgenic skinny mice relative to nontransgenic littermates. The BP elevation in transgenic skinny mice is abolished by alpha(1)-adrenergic, beta-adrenergic, or ganglionic blockers at doses that do not affect BP in nontransgenic littermates. Central administration of an alpha-melanocyte-stimulating hormone antagonist causes a marked increase in cumulative food intake but no significant changes in BP. The obese KKA(y) mice develop BP elevation with increased urinary catecholamine excretion relative to control KK mice. After a 2-week caloric restriction, BP elevation is reversed in nontransgenic littermates with the A(y) allele, in parallel with a reduction in plasma leptin concentrations, but is sustained in transgenic mice overexpressing leptin with the A(y) allele, which remain hyperleptinemic. This study demonstrates BP elevation in transgenic skinny mice and obese KKA(y) mice that are both hyperleptinemic, thereby suggesting the pathophysiological role of leptin in some forms of obesity-related hypertension.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; alpha-MSH; Animals; Blood Pressure; Body Weight; Eating; Energy Intake; Ganglionic Blockers; Heart; Heart Rate; Hexamethonium; Hypertension; Kidney; Leptin; Male; Melanocyte-Stimulating Hormones; Mice; Mice, Transgenic; Models, Biological; Obesity; Organ Size; Sympathetic Nervous System; Systole; Urine

Environmental factors and diet are generally believed to be accelerators of obesity and hypertension, but they are not the underlying cause. Our animal model of obesity and hypertension is based on the observation that impaired fetal growth has long-term clinical consequences that are induced by fetal programming. Using fetal undernutrition throughout pregnancy, we investigated whether the effects of fetal programming on adult obesity and hypertension are mediated by changes in insulin and leptin action and whether increased appetite may be a behavioral trigger of adult disease. Virgin Wistar rats were time mated and randomly assigned to receive food either ad libitum (AD group) or at 30% of ad libitum intake, or undernutrition (UN group). Offspring from UN mothers were significantly smaller at birth than AD offspring. At weaning, offspring were assigned to one of two diets [a control diet or a hypercaloric (30% fat) diet]. Food intake in offspring from UN mothers was significantly elevated at an early postnatal age. It increased further with advancing age and was amplified by hypercaloric nutrition. UN offspring also showed elevated systolic blood pressure and markedly increased fasting plasma insulin and leptin concentrations. This study is the first to demonstrate that profound adult hyperphagia is a consequence of fetal programming and a key contributing factor in adult pathophysiology. We hypothesize that hyperinsulinism and hyperleptinemia play a key role in the etiology of hyperphagia, obesity, and hypertension as a consequence of altered fetal development.

Topics: Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Birth Weight; Blood Pressure; Eating; Energy Intake; Fasting; Female; Fetus; Hyperphagia; Hypertension; Insulin; Leptin; Nutrition Disorders; Obesity; Pregnancy; Pregnancy Complications; Rats; Rats, Wistar

There is substantial evidence that obesity is a prime risk factor for the development of hypertension. Although hyperinsulinemia and an increased activity of the sympathetic nervous system have been implicated in the pathogenesis of "obesity hypertension," their effects on energy metabolism have not been studied thus far. In the present study, we therefore examined resting metabolic rate (RMR) and basal substrate oxidation in subjects with obesity and obesity-related hypertension. A total of 166 subjects were characterized for RMR and basal substrate use through indirect calorimetry. Blood pressure was measured at rest and with 24-hour ambulatory monitoring. Blood samples were collected for the measurement of plasma catecholamines, leptin, and the insulin response to an oral glucose load. In our study population, 116 subjects were defined as hypertensive and 91 were defined as obese. Hypertensive patients under beta-adrenergic blockade (n=42) had a significantly lower RMR than did patients without beta-blockade (P<0. 05) and were therefore excluded from further analyses. Univariate regression analysis revealed a significant relationship between RMR and body fat mass, as well as body fat-free mass, in both groups. Compared with obese normotensive control subjects (n=27), obese hypertensives (n=43) had a 9% higher RMR (P<0.05), higher plasma catecholamine (P<0.05) and leptin (P<0.05) levels, and an increased insulin response to oral glucose (P<0.01). Together, these findings are compatible with the idea that chronic neurogenic and metabolic adaptations related to obesity may play a role in the development of obesity hypertension in susceptible individuals.

Topics: Adult; Aged; Basal Metabolism; Catecholamines; Energy Metabolism; Female; Humans; Hypertension; Insulin; Leptin; Male; Middle Aged; Obesity; Oxidation-Reduction; Regression Analysis

The number of patients with hypertension, obesity, diabetes, and hyperlipidemia is increasing. This tendency is observed in pregnant women, in whom many obstetrical and perinatal complications occur. The prevention of these abnormalities is important in reducing perinatal mortality and the risk of coronary disease. We established a pregnant rat model with diabetes and signs and symptoms mimicking preeclampsia. On day 6 of pregnancy, streptozotocin (STZ) or citrate buffer was injected into the tail vein. After STZ administration, plasma glucose was increased within 48 hours and sustained at a high level until day 20 of pregnancy, and plasma insulin was decreased. Fetuses from STZ-treated mothers were growth-restricted, and plasma glucose was 6-fold higher in fetuses of STZ-treated versus control rats. The systolic blood pressure, urinary protein, and hematocrit were increased significantly in STZ-treated rats. Total cholesterol and triglycerides were also elevated in STZ-treated rats, but plasma leptin levels were decreased. The STZ-induced diabetic pregnant rat model exhibited preeclampsia, hemoconcentration, hyperlipidemia, hypoleptinemia, and intrauterine growth restriction. This model closely mimics the features of human pregnancy complicated by diabetes and is useful for the basic study of the pathophysiology of pregnancy with diabetes.

Topics: Animals; Diabetes Mellitus, Experimental; Disease Models, Animal; Female; Hypertension; Leptin; Pre-Eclampsia; Pregnancy; Pregnancy in Diabetics; Rats; Rats, Wistar; Streptozocin

The purpose of this study was to clarify the relationships between obesity (BMI) and BP levels, leptin levels, sympathetic activity, and insulin sensitivity in a Japanese male population. In 912 young, non-diabetic, Japanese men with a wide range of BMI (16.5-33.6 kg/m2), blood pressure (BP), fasting plasma norepinephrine (NE), insulin and leptin levels were measured after an overnight fast. The cohort consisted of 603 normotensive and 309 hypertensive subjects. The study was carried out using a cross-sectional design. When the subjects were subdivided by tertile in relation to BMI, the 101 subjects in the heaviest group (BMI > 27.9 kg/m2) had a significantly higher systolic BP (p< 0.05) and pulse rate (p< 0.05) as well as higher NE (p< 0.01), insulin (p< 0.01), and leptin (p< 0.01) levels than 86 subjects in the leanest group (BMI < 22.2 kg/m2). In the whole cohort, BMI correlated with mean BP (p< 0.01), plasma NE (p< 0.05), insulin (p< 0.001) and leptin (p< 0.001). The mean BP correlated with BMI (p< 0.001), plasma NE (p< 0.01), insulin (p< 0.01) and leptin (p< 0.05). Plasma leptin levels correlated with fasting plasma insulin levels (p < 0.05), but not with plasma NE levels (NS). As analyzed by multiple regression analysis, only plasma NE (p< 0.05) and BMI (p< 0.001), but not plasma insulin levels, were significant, independent predictors of BP levels (r2=0.125, F= 10.51, p=0.0001). These results suggest that obesity (BMI) and heightened sympathetic nervous system activity contribute to BP elevation (hypertension).

Topics: Adult; Blood Pressure; Body Mass Index; Cohort Studies; Cross-Sectional Studies; Fasting; Humans; Hypertension; Insulin; Leptin; Male; Middle Aged; Norepinephrine; Obesity; Reference Values; Sympathetic Nervous System

Leptin, the gene product of the ob gene, is influenced by gender and insulin sensitivity. Because in human hypertension there are important endocrine-hemodynamic gender-dependent differences, we compared plasma leptin in 39 essential hypertensives (EH) and in 27 normotensive healthy subjects (HS) matched for gender, age, and fat mass. Fat mass was measured by bioelectrical impedance analysis (BIA), plasma leptin by a sensitive radioimmunoassay RIA (intraassay CV < 6%), and insulin sensitivity by the HOMA-R index. Both in essential hypertensives and in normotensive subjects plasma leptin was consistently higher in females than in males and was strictly related to fat mass. Gender differences in plasma leptin were not explained by differences in fat mass. Separate analysis of data by gender showed that leptin was significantly higher (P < .05) in hypertensive men (median, 5.4 ng/mL; interquartile range, 4.1-9.5) than in normotensive men (4.6 ng/mL, 2.6-7.4) whereas it was identical in hypertensive and normotensive women. In essential hypertensives, in a multiple regression model only fat mass, gender, and the HOMA-R index were independently linked to plasma leptin. Similarly, fat mass and gender were independent predictors of plasma leptin in normotensive subjects. In the combined group of hypertensive and normotensive men, heart rate as well as systolic and diastolic pressure were univariate predictors of leptin. However, in a multivariable model only heart rate was independently related to leptin, and neither systolic nor diastolic pressure contributed significantly to explain the variability in plasma leptin. No relationship was found between leptin and heart rate or systolic or diastolic pressure in women. These results support the notion that leptin may participate in the gender-dependent variability of human hypertension.

Topics: Female; Hemodynamics; Humans; Hypertension; Leptin; Male; Middle Aged; Multivariate Analysis; Sex Factors

Leptin and TNF alpha are thought to influence blood pressure. Therefore, the aim of our study was to investigate leptin and TNF alpha levels and their association with blood pressure, sex steroids, insulin, creatinine and lipids in type 2 diabetic patients. In 424 type 2 diabetic patients (79 hypertensive females [+Hf], 79 normotensive females [-Hf]; 133 hypertensive males [+Hm], 133 normotensive males [-Hm]) matched for sex, age and BMI serum leptin levels were measured by RIA and TNF alpha, insulin, estradiol, progesterone by ELISA as well as free testosterone by RIA. Leptin levels were comparable in +Hf and -Hf (16.5 +/- 1.0 microg/l vs 16.3 +/- 1.0 microg/l) but higher in +Hm as compared to -Hm (8.3 +/- 0.47 microg/l vs 6.5 +/- 0.34 microg/l; p<0.05). In addition, in comparison to -Hm serum levels of insulin (190 +/- 10 pmol/l vs 161 +/- 11 pmol/l; p< 0.005) and also of creatinine (118.6 +/- 3.6 micromol/l vs 101.7 +/- 2.3; p< 0.0001) were higher in +Hm. Pearson's Correlation coefficient revealed a positive correlation between levels of leptin and diastolic blood pressure (p<0.05) and also between leptin and insulin (p<0.001) in males, however, only before correction for BMI. No correlation between leptin and creatinine was found in males and females. Levels of TNF alpha were comparable in all subgroups. No correlation between levels of TNF alpha and serum leptin levels, blood pressure and insulin was found. In females TNF alpha was positively correlated with creatinine (p<0.001) and in males positively with progesterone (p<0.001). Taken together, higher serum leptin levels were found in hypertensive type 2 diabetic males as compared to normotensives, which may be related to the BMI and higher levels of insulin. These findings are accompanied by a trend to lower levels of free testosterone in hypertensive type 2 diabetic males. TNF alpha levels were comparable in female and male hypertensive and normotensive type 2 diabetic subjects.

Topics: Aged; Body Mass Index; Creatinine; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Humans; Hypertension; Insulin; Leptin; Male; Reference Values; Testosterone; Tumor Necrosis Factor-alpha

Both leptin and the renin-angiotensin system (RAS) can influence the activity of the sympathetic nervous system, water and electrolyte metabolism as well as vascular remodelling, which are all involved in the regulation of arterial blood pressure. Thus leptin and the RAS may act together in the pathogenesis of essential hypertension. The present study aimed to answer the following question: does an interrelationship exist between leptinaemia and the plasma renin activity (PRA) profile in normotensive and hypertensive subjects? Forty-three patients with essential hypertension (EHP) (23 females, 20 males, mean age 39.0 +/- 1.8 years, mean body mass index (BMI) 26. 8 +/- 0.6 kg/m2, mean arterial pressure (MAP) 123 +/- 2 mm Hg) and 32 healthy subjects (NTS) (18 females, 14 males, mean age 38.6 +/- 2. 2 years, mean BMI 25.4 +/- 0.5 kg/m2, MAP 95 +/- 1 mm Hg) were examined. Plasma leptin levels were estimated once after the administration of a diet containing 100-120 mmol Na/day and after overnight 8-h recumbency. PRA was estimated twice: first after the administration of a diet containing 100-120 mmol Na day and overnight 8-h recumbency (PRA I), and a second time after 3 days of sodium restriction (20 mmol Na/day), and 3 h of upright position (PRA II). Antihypertensive drugs were withdrawn 7 days before the study. In EHP plasma leptin concentration was insignificantly higher than in NTS (14.0 +/- 2.0 vs10.8 +/- 1.5 ng/ml respectively). Only females with hypertension showed a significant positive correlation between plasma leptin concentrations (expressed as the logarithmic values) and PRA I. Using the multiple regression analysis, in all studied subjects (EHP and NTS together), logarithm (log) of plasma leptin concentrations was significantly related to gender, BMI and MAP. Multiple regression analysis performed separately for EHP or NTS revealed a significant relation of log plasma leptin concentrations with gender and BMI. A significant correlation was found between log leptinaemia values and BMI, mean and systolic blood pressure respectively if the whole group of subjects (EHP+NTS) or EHP and NTS separately were analysed. Especially in hypertensive women a highly significant correlation was found between log plasma leptin concentrations and MAP. We conclude that a significant relationship between leptinaemia and PRA does exist in females with EH and that participation of both PRA and leptin in the pathogenesis of EH in females seems to be likely.

Topics: Adult; Blood Pressure; Female; Humans; Hypertension; Leptin; Male; Reference Values; Renin; Sex Characteristics; Systole

To assess the independent and joint effects of the components of the metabolic syndrome, including leptin, which is a recently proposed addition to this syndrome, in predicting the cumulative incidence of impaired glucose tolerance (IGT) and diabetes among individuals with normal glucose tolerance.. This prospective study involved 2,605 residents of Mauritius with normal glucose tolerance who were followed for 5 years for IGT or diabetes onset in relation to total and regional adiposity (BMI, waist-to-hip ratio [WHR]), fasting and 2-h 75-g oral glucose load glucose and insulin, total and HDL cholesterol, blood pressure, serum uric acid, triglyceride, and leptin levels.. A multivariate logistic regression model adjusted for age, sex, ethnicity, and diabetes family history showed a significantly higher linear increase in risk of IGT and diabetes in association with the following variables only: fasting glucose (odds ratio 1.89 [95% CI 1.51-2.34]), 2-h glucose (1.68 [1.50-1.88]), WHR (1.30 [1.10-1.52]), BMI (1.04 [1.00-1.08]), and serum uric acid (1.37 [1.20-1.57]). However, a nonlinear increase was seen with serum triglyceride and plasma leptin concentrations. No risk factors resulted in joint effects that were greater than expected from combining individual effects.. Metabolic syndrome features independently predict a higher risk of diabetes or IGT in normoglycemic subjects but in combination confer no higher-than-expected risk of these outcomes. At higher concentrations of triglycerides and leptin, risk plateaus and even declines slightly.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Ethnicity; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Hyperlipidemias; Hypertension; Insulin; Leptin; Longitudinal Studies; Male; Mauritius; Middle Aged; Multivariate Analysis; Prospective Studies; Racial Groups; Regression Analysis; Risk Factors; Syndrome; Time Factors

We compared the effects of hypothalamic obesity induced by neonatal monosodium glutamate (MSG) treatment between spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). Newborn WKY and SHR were injected intraperitoneally with 4 mg/kg body weight of MSG daily for 5 days. At 6 months of age, the obesity of SHR was more advanced than that of WKY, but at 14 months of age the severity of obesity was similar between the two strains. Hypertriglyceridemia was enhanced in MSG-treated SHR as compared with MSG-treated WKY. Systolic blood pressure measured by the tail-cuff method was consistently lower in MSG-treated SHR than in control SHR, whereas blood pressure was not affected by neonatal MSG treatment in WKY. Food restriction reduced body weight more in control SHR than in control WKY, with the former also showing enhanced ketogenesis. Neonatal MSG treatment abolished the accelerated reduction of body weight in SHR. Serum leptin concentration was markedly increased in MSG-treated obese rats, though no differences were seen between WKY and SHR in the control or MSG-treated groups. Serum leptin was closely correlated with both Lee obese index and mesenteric fat weight over the strain. Blood flow in interscapular brown adipose tissue (BAT) measured by Laser Doppler flowmetry was significantly increased in response to beta3-adrenoceptor agonist BRL26830A in both the control and MSG-treated rats. However, the response of blood flow was not affected by MSG treatment or strain difference. The present study demonstrated some strain differences in response to neonatal MSG treatment between WKY and SHR. These differences could not be explained by the difference in serum leptin level or beta3-adrenergic reactivity in BAT.

Topics: Adipose Tissue, Brown; Adrenergic beta-3 Receptor Agonists; Adrenergic beta-Agonists; Animals; Blood Pressure; Disease Models, Animal; Energy Intake; Ethanolamines; Female; Food Additives; Hypertension; Leptin; Male; Obesity; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Regional Blood Flow; Sodium Glutamate; Weight Loss

Leptin, a peptide hormone produced mainly in fat cells, appears to be important for the regulation of metabolism, insulin secretion/sensitivity and body weight. Recently, elevated plasma leptin levels have been reported in patients with arterial hypertension. Because a change in circulating leptin concentrations in such patients could be caused by altered rates of production or disposal, or both, the aim of the present study was to identify regions of leptin overflow into the bloodstream and of leptin extraction. Patients with arterial hypertension (n=12) and normotensive controls (n=20) were studied during catheterization with elective blood sampling from different vascular beds (artery, and renal, hepatic, iliac and cubital veins). Plasma leptin was determined by a radioimmunoassay. Patients with hypertension had significantly elevated levels of circulating leptin (12.8 ng/l, compared with 4.1 ng/l in the controls; P<0.001), and this was also the case when adjusted for body mass index (BMI) [0.435 and 0.167 ng/l per unit BMI (kg/m(2)) respectively; P<0.001]. Circulating leptin was directly related to arterial blood pressure (r=0.38-0.62, P

Topics: Adult; Aged; Blood Pressure; Body Mass Index; Case-Control Studies; Female; Humans; Hypertension; Insulin; Kidney; Least-Squares Analysis; Leptin; Liver; Male; Middle Aged; Radioimmunoassay; Renin; Statistics, Nonparametric

Studies, comparing several disease-prone and disease-resistant rat strains to elucidate the extent and severity of syndromes resembling human diseases are lacking. Therefore we studied the inbred rat strains BB/OK, BN/Crl, LEW/K and WKY/Crl in comparison with SHR/Mol and WOKW/K rats as models of metabolic syndrome.. Body weight and body mass index (BMI) were measured in 12 males of each strain at 14 weeks. In addition blood glucose, serum triglycerides, cholesterol, insulin and leptin were determined at 12, 13 and 14 weeks of age.. In contrast to SHR animals, WOKW rats develop a severe metabolic syndrome including obesity, hyperleptinemia, hyperinsulinemia and dyslipidemia.. We conclude that; (i) the choice of disease-resistant inbred rat strains as 'healthy controls' for a disease-prone strain has to be carefully evaluated; (ii) in comparison with SHR, WOKW rats develop most if not all facets of the metabolic syndrome described in human and (iii) as with the human disease the syndrome in rats is polygenic.

Topics: Animals; Blood Glucose; Body Mass Index; Body Weight; Cholesterol; Glucose Intolerance; Hyperlipidemias; Hypertension; Insulin; Insulin Resistance; Leptin; Male; Obesity; Quality Control; Rats; Rats, Inbred BB; Rats, Inbred BN; Rats, Inbred Lew; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Triglycerides

The author exposes the present concept of metabolic syndrome X, which is a complex of Type II diabetes, obesity, hypertension and vascular problems. This syndrome has been known for many years, but it has been individualized as such only recently. This is due to the huge importance that obesity is reaching in developed countries, especially in the U.S.A. Today this is a very important health problem. In this work, in addition to the description of the syndrome, which is purely an internal medicine issue, its relation to some women-specific problems is also explained, especially to the so-called polycystic ovary.

Topics: Diabetes Mellitus; Diabetes Mellitus, Type 2; Female; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Leptin; Menopause; Myocardial Ischemia; Obesity; Phenotype; Polycystic Ovary Syndrome; Syndrome

The aim of the study was to investigate cord blood leptin concentrations and their relationship to birth weight and gender in term pregnancies complicated by pre-eclampsia. Cord blood samples were obtained from 52 women, identified as having pre-eclampsia, and their newborns (31 males and 21 females) immediately after birth. Specimens were analyzed using a human leptin 125I radioimmunoassay. The relationship between leptin and anthropometrics was assessed by Spearman correlation. Differences in cord blood leptin levels between male and female infants were tested with the Mann-Whitney U test. The correlation between leptin and gender was computed using the product-moment-biseral correlation analysis for continuous and dichotomous variables. The multiple logistic regression analysis examined influences of sex, birth length, birth weight, birth weight/birth length ratio, ponderal index and maternal leptin as covariates on the fetal cord leptin level. Fetal leptin correlated positively with birth weight, length and weight/length ratio, in the total group and in the male subgroup and additionally with ponderal index in the female subgroup. Cord blood leptin concentrations in female newborns were significantly higher than in male newborns (p = 0.015), and concentrations correlated with gender (r = -0.315; p = 0.023). Multiple logistic regression analysis revealed four potential independent factors influencing fetal cord leptin: gender, birth weight, birth weight/birth length ratio and maternal leptin. In conclusion, cord leptin concentrations in pregnancies complicated by pre-eclampsia correlate positively with birth weight and gender. Leptin concentrations in female newborns are higher compared to male newborns.

Topics: Adult; Antihypertensive Agents; Birth Weight; Female; Fetal Blood; Gestational Age; Humans; Hypertension; Infant, Newborn; Labetalol; Leptin; Magnesium; Male; Multivariate Analysis; Pre-Eclampsia; Pregnancy; Proteinuria; Regression Analysis; Sex Factors

This cross sectional study was undertaken to determine whether serum leptin levels were associated with multiple risk factor (MRF) clustering syndrome. We examined the relationship between serum leptin concentrations and blood pressure (BP), serum lipids levels, calculated insulin resistance (HOMA-ratio) and adiposity among 581 Japanese adult women. The serum leptin was increased in female subjects with systolic (> or =160 mmHg) and diastolic > or =90 mmHg) hypertension compared with the normotensive females (mean+/-SE; 9.3+/-0.5 vs 7.7+/-0.3; 10.2+/-0.6 vs 7.1+/-0.3 ng/ml, both p<0.001). Serum leptin was elevated in those with hyper-cholesterolemia (C; > or =220 mg/dl) and triglyceridemia (TG; > or =150 mg/dl) compared with the normolipidemia (9.4+/-0.4 vs 7.8+/-0.3; 11.7+/-0.6 vs 7.5+/-0.2 ng/ml, both p <0.001). Serum leptin was also elevated in those with adiposity (BMI > or =26.4 kg/m2) and insulin resistance (HOMA-ratio > or =2.5) compared with the normal females (14.8+/-0.7 vs 5.2+/-0.2; 11.3+/-1.1 vs 7.1+/-0.4ng/ml, both p<0.001). Even after adjusting for BMI or percent body fat mass (BFM), leptin levels remained to be elevated significantly in all these diseases. There was a positive correlation between serum leptin and systolic, diastolic BP, TC, TG, BMI, BFM, IRI and HOMA-ratio (r=0.12, p=0.005; r=0.24, p<0.0001; r=0.19, p<0.0001; r=0.35, p<0.0001; r=0.72, p<0.0001; r=0.73, p<0.0001; r=0.47, p< 0.0001; r=0.44, p<0.0001), and a negative correlation with HDL-C levels (r= -0.20, p< 0.0001). These correlations were also observed in leptin levels after adjusting for the BMI or BFM. Multiple regression analysis showed that BFM, HOMA-ratio and TG were significant determinants of leptin concentration before (t=12.6, p<0.0001; t=3.33, p=0.001; t=3.22, p=0.001) and after adjusting for BMI or BFM. These results suggest that because serum leptin levels were elevated in components of MRF clustering syndrome, leptin may have a pathophysiological role in MRF clustering syndrome.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Arteriosclerosis; Blood Pressure; Body Mass Index; Cholesterol; Cross-Sectional Studies; Female; Humans; Hyperlipidemias; Hypertension; Insulin Resistance; Japan; Leptin; Middle Aged; Obesity; Risk Factors; Syndrome; Triglycerides

Topics: Animals; Body Weight; Embryonic and Fetal Development; Female; Humans; Hypertension; Infertility; Leptin; Pregnancy; Pregnancy Complications, Cardiovascular

We determined the serum levels of leptin in 96 pregnant women with body mass index between 20 to 30, 30 normal (NP), 26 with mild preeclampsia (MPE), 27 with severe preeclampsia (SPE), 6 with chronic hypertension plus preeclampsia (CHT+PE) and 7 with chronic hypertension (CHT). A significant (p < 0.01) decrease in leptin levels was observed in the SPE group when compared with the NP group. On the contrary, significant (p < 0.05) increases were observed in the CHT and CHT+PE groups when compared with the NP group. Leptin levels were significantly higher in the MPE (p < 0.001), CHT (p < 0.01) and CHT+PE (p < 0.5) groups when compared with the SPE. No significant differences were observed in the CHT group when compared with CHT+PE. Moreover, a positive correlation was encountered (r = 0.6, p < 0.001) between platelet number and leptin levels for all the patients with preeclampsia. These results suggest that leptin levels may be useful metabolic parameter in different types of hypertension during pregnancy.

Topics: Adult; Case-Control Studies; Female; Humans; Hypertension; Leptin; Platelet Count; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Cardiovascular

Leptin, important for body weight regulation, may be involved in the pathogenesis of the insulin resistance syndrome, associated with cardiovascular disease. We tested to determine whether leptin is a risk marker for first-ever stroke in a nested case-referent study.. We identified 113 patients with first-ever stroke (94 with ischemic and 19 with hemorrhagic stroke) who, before the stroke, had participated in population-based health surveys in northern Sweden. Referents were matched for sex, age, date and type of health survey, and geographic region. Blood pressure (BP), body mass index (BMI), and presence of smoking, diabetes, and hypertension were recorded. Total cholesterol, insulin, and leptin were analyzed in stored samples. Risk markers for first-ever stroke were analyzed by conditional logistic regression analysis.. Patients with hemorrhagic stroke had higher levels of BMI and systolic and diastolic BPs. Leptin levels were 72% and 59% higher in males and females, respectively, with hemorrhagic stroke versus referents. Patients with ischemic stroke more often had hypertension, diabetes mellitus, and higher fasting glucose and insulin levels. A diagnosis of hypertension and elevated systolic and diastolic BPs were significant risk markers for first-ever hemorrhagic stroke in univariate analysis. High leptin (OR=20.55; 95% CI, 1.12 to 376.7) levels together with hypertension (OR=16.28; 95% CI, 1.49 to 177.3) remained as significant risk markers in a multivariate model. The combination of high leptin and high systolic or diastolic BP were associated with a profoundly increased risk for hemorrhagic stroke (OR=22.11; 95% CI, 1.57 to 310.9). Diabetes, hypertension, and obesity (BMI >/=27), together with high levels of insulin, glucose, systolic and diastolic BP, were significant risk markers for first-ever ischemic stroke in univariate analysis. Hypertension (OR=2.10; 95% CI, 1.14 to 3.86) remained as an independent risk marker in a multivariate model.. Plasma leptin is strongly associated with an increased risk for first-ever hemorrhagic stroke, independent of other risk markers for cardiovascular disease. Leptin may be an important link in the development of cardiovascular disease in obesity.

Topics: Adult; Aged; Biomarkers; Blood Pressure; Body Mass Index; Brain Ischemia; Cerebral Hemorrhage; Cohort Studies; Female; Humans; Hypertension; Incidence; Leptin; Male; Middle Aged; Obesity; Population Surveillance; Prognosis; Proteins; Retrospective Studies; Risk Factors; Sweden

This paper is a summary of results obtained in our studies on leptinemia in patients with chronic renal failure treated with recombinant human erythropoietin (rHuEPO), in kidney transplant patients, in patients with essential hypertension, and in pregnant women with preeclampsia. In this study, we found that rHuEPO treatment has a suppressive effect on leptinemia in patients with endstage renal failure. These results suggest that the appetite stimulating effect of rHuEPO may be mediated by a reduction of leptin synthesis and release. At the early stage of successful kidney transplantation, a significant decline of leptinemia was noticed, which was not related either to the excretory function of the graft or the kind and dose of immunosuppressants. In kidney transplant patients with grafts functioning well for 2.5 years, significantly elevated leptinemia was found. From these results, we may conclude that factors other than the excretory function of the graft and the kind and dosage of immunosuppressants may be involved in the pathogenesis of abnormal leptinemia in these patients. Both in normotensive subjects and patients with essential hypertension, a positive correlation was found between leptinemia and mean blood pressure, suggesting that leptin may be involved in the regulation of blood pressure. Both healthy and preeclamptic pregnant women show higher leptinemia than nonpregnant women. In preeclamptic women, leptin levels in maternal vein blood, umbilical cord blood, and amniotic fluid were significantly higher than respective values found in healthy pregnant women. In contrast to healthy pregnant and nonpregnant women, in women with preeclampsia, no correlation was found between the body mass index (BMI) and leptinemia. In preeclamptic women the abnormally elevated leptinemia was not related to blood pressure. Finally, no correlation was found between leptinemia in maternal and umbilical cord blood. From these studies, it follows that the elucidation of abnormal leptin secretion in the pathogenesis of preeclampsia needs further study.

Topics: Adipose Tissue; Amniotic Fluid; Appetite; Blood Pressure; Blood Proteins; Body Mass Index; Erythropoietin; Female; Fetal Blood; Humans; Hypertension; Immunosuppressive Agents; Kidney Failure, Chronic; Kidney Transplantation; Leptin; Pre-Eclampsia; Pregnancy; Proteins

This cross-sectional study aimed to evaluate the relationship between leptin and the cluster of abnormalities often referred to as the metabolic syndrome. The serum leptin concentration, body mass index (BMI), percent body fat, total fat mass (FM), waist and hip circumference, waist to hip ratio (WHR), prevalence of hypertension, and triglyceride (TG), lipoprotein, and uric acid concentration were determined in 86 type 2 diabetic (n = 59) and healthy (n = 27) subjects. Multiple regression analyses showed that the estimates of total body obesity (BMI, percent body fat, and total FM), sex, and serum uric acid concentration are independently associated with the serum leptin concentration. The finding of a positive correlation between serum leptin and uric acid levels suggests that leptin could be a pathogenic factor responsible for hyperuricemia in obesity.

Topics: Adipose Tissue; Analysis of Variance; Body Constitution; Body Mass Index; Case-Control Studies; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Female; Humans; Hypertension; Leptin; Linear Models; Lipoproteins; Male; Middle Aged; Obesity; Proteins; Sex Factors; Syndrome; Triglycerides; Uric Acid

Previous studies demonstrated elevated plasma leptin and angiotensinogen (PRA) levels in essential hypertension. However, a few studies investigated the relationship between leptin and angiotensinogen levels in both lean and overweight/ obese hypertensives. The aim of the present study was therefore to examine the relationship between blood pressure, leptin and plasma renin activity in normotensives and in both lean and overweight/obese patients with essential hypertension. Two groups of subjects who were carefully matched for age, gender, waist:hip ratio and body mass index (BMI) were studied: 28 normotensives (NT) (age: 40.1+/-9.1 years old, BMI: 28.1+/-3.6 kg/m2, male/female: 18/10) and 33 newly diagnosed mild to moderate essential hypertensives (EHT) (age: 38.9+/-10 years old, BMI: 27.9+/-4.8 kg/m2, male/female: 22/11). No significant differences in age, gender, waist:hip ratio, fasting blood glucose and BMI were detected between EHT and NT groups. However, systolic and diastolic pressures, mean arterial blood pressures, plasma leptin levels and PRA were significantly higher in EHT group than in NT group (P = 0.001). Plasma leptin levels were strongly correlated with BMI in EHT (r=0.67, P = 0.001) and NT groups (r=0.44, P = 0.001). Plasma leptin levels were correlated with plasma PRA levels in both EHT and NT groups (r = 0.66 and r = 0.44; both P < 0.05, respectively). There was no correlation between leptin or PRA and systolic, diastolic pressures, or mean arterial blood pressures. Furthermore, the patients were divided as lean (n=16) and overweight/obese (n = 17) and compared with BMI-matched controls. In both subgroups, plasma leptin and PRA levels were also higher than those of controls. Our results showed that elevated plasma leptin and PRA are associated with hypertension in both lean and overweight/obese hypertensives. Moreover, plasma leptin was significantly correlated with plasma angiotensinogen levels. These findings suggest that adipose mass is an important determinant of blood pressure, although the mechanism is not clear.

Topics: Adult; Blood Pressure; Body Mass Index; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Proteins; Renin

Previous studies on humans have reported higher leptin levels in women than in men, independent of body fat, and leptin has been correlated with insulin resistance in men but not in women. Since insulin resistance is thought to play a role in raising blood pressure, we investigated sex differences in leptin concentrations between hypertensive and normotensive individuals.. Ninety-two nondiabetic hypertensive patients (48 men and 44 women) and 92 age, body mass index (BMI)-matched normotensive control individuals were studied. Fasting plasma glucose, insulin, leptin and lipoprotein concentrations, glucose and insulin responses to 75 g oral glucose tolerance test (OGTT) and insulin suppression tests were determined.. Fasting plasma leptin concentrations were higher in hypertensive men than in normotensive men (5.1 +/- 0.5 versus 3.9 +/- 0.4 ng/ml, P = 0.015). However, fasting plasma leptin concentrations were not significantly different between hypertensive and normotensive women (11.8 +/- 1.0 versus 10.9 +/- 1.0 ng/ml, P = 0.440). Fasting plasma leptin concentrations showed good correlation with BMI, body fat, fasting plasma insulin concentrations, and insulin area to OGTT in both men and women (all P < 0.001). However, fasting plasma leptin concentrations were related to steady-state plasma glucose (SSPG) concentrations, a measure of insulin sensitivity by insulin suppression test, in men only (P < 0.001). After adjustment for body fat amount, age and duration of hypertension, fasting plasma leptin levels still correlated significantly with SSPG concentrations in men. These four variables together accounted for a 67.9% variation in fasting plasma leptin levels in men. In women, body fat amount was the only significant determinant for plasma leptin levels. These four variables accounted for a 78.2% variation in plasma leptin levels in women.. Our study confirmed a sex difference in leptin levels both in hypertensive and normotensive subjects. Higher plasma leptin concentrations in hypertensive men but not in hypertensive women when compared with normotensive control individuals was also demonstrated. These observations are consistent with the findings that plasma leptin is correlated with insulin sensitivity in men but not in women. Further studies are needed to understand the causes and consequences of sex effects on leptin in blood pressure regulation.

Topics: Adipose Tissue; Age Factors; Antihypertensive Agents; Blood Glucose; Blood Pressure; Body Composition; Body Mass Index; Electric Impedance; Female; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Regression Analysis; Sex Factors

Leptin levels are elevated in end-stage renal disease, suggesting an impairment of renal leptin degradation. The present study aimed to determine whether leptin levels are also elevated in patients with earlier stages of renal disease, ie, microalbuminuric and macroalbuminuric nephropathy. A total of 60 subjects were assigned to two study groups. Group A contained 10 type 2 diabetics with macroalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy control subjects. Group B contained 10 type 2 diabetics with microalbuminuria, 10 type 2 diabetics with normoalbuminuria, and 10 healthy controls. The subgroups of both study groups were matched for sex and body fatness. In group A, macroalbuminuric diabetic patients had higher serum leptin levels than the normoalbuminuric diabetics (11.90 +/- 2.98 v 4.13 +/- 0.92 ng/mL, P < .002) and control subjects (4.78 +/- 1.37 ng/mL, P < .006). In group B, microalbuminuric diabetics had higher serum leptin levels than the normoalbuminuric diabetics (21.16 +/- 5.80 v8.74 +/- 1.89 ng/mL, P < .04) and control subjects (10.06 + 3.00 ng/mL, P < .06). In both groups A and B, creatinine clearance was inversely correlated with the serum leptin level after adjusting for body fat. In conclusion, serum leptin levels are elevated in type 2 diabetic patients with microalbuminuria and macroalbuminuria, suggesting that renal leptin degradation is already impaired in the early stages of renal disease.

Topics: Adipose Tissue; Aged; Albuminuria; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Creatinine; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Reference Values; Triglycerides

Plasma leptin levels and plasma insulin levels have been found to be elevated in patients with essential hypertension (EH) and have been suggested to be components of the metabolic syndrome. Increased heart rate (HR) may predict the development of EH in normal or borderline-hypertensive individuals. The aim of our study was to test the hypothesis that elevated plasma leptin and insulin levels as well as systolic blood pressure (SBP) and diastolic blood pressure (DBP) and increased resting HR preexist in the healthy offspring of patients with EH.. Twenty-six (12 male, 14 female) healthy offspring of hypertensive patients, mean age 16 +/- 2.5 years and body mass index (BMI) of 21.5 +/- 2.8 kg/m(2) (group A), and 30 (14 male, 16 female) healthy offspring of normotensive patients, mean age 17 +/- 2.3 years and BMI of 21.9 +/- 2.4 kg/m(2) (group B), were studied. (The two groups were matched for sex, age, and BMI). Mean SBP, DBP, resting HR, plasma leptin, and plasma insulin levels (radioimmunoassay method) were determined in the whole study population. Mean SBP, DBP, and resting HR were significantly higher in group A than in group B (120 +/- 12 vs 112 +/- 9.5 mm Hg, 77 +/- 9 vs 72 +/- 7 mm Hg, 79 +/- 8 vs 75 +/- 5 beats/min, P <.01, P <.05, and P <.05, respectively). Plasma leptin and insulin levels were significantly higher in group A than in group B (9 +/- 5.06 vs 5.6 +/- 2.5 ng/mL and 20.11 +/- 11.3 vs 14.8 +/- 5.2 microIU/mL, P <.01 and P <.05, respectively).. Our findings support the hypothesis that hyperleptinemia, hyperinsulinemia, and elevated blood pressure and resting HR preexist in the healthy offspring of patients with EH.

Topics: Adolescent; Biomarkers; Blood Pressure; Female; Genetic Predisposition to Disease; Heart Rate; Humans; Hyperinsulinism; Hypertension; Insulin; Leptin; Male; Radioimmunoassay

Leptin, the product of the ob gene, has been shown to increase heart rate and blood pressure through a stimulation of cardiac sympathetic nervous system activity, a phenomenon also involved in the pathogenesis of left ventricular hypertrophy in hypertensives. Thus, we hypothesize that plasma leptin concentration is associated with left ventricular hypertrophy. Forty hypertensive males and 15 healthy male subjects underwent anthropometric and echocardiographic evaluations, assessment of insulin sensitivity through euglycemic glucose clamp combined with indirect calorimetry, and determination of fasting plasma leptin concentration. Fasting plasma leptin levels were higher in hypertensives than in controls (6.48+/-2.9 versus 4. 62+/-1.5 ng/mL, P<0.05); these results were unchanged after adjustment for body mass index (P<0.05). In the whole group of patients (n=55), fasting plasma leptin concentration was correlated with body mass index (r=0.46, P<0.001) and waist/hip ratio (r=0.50, P<0.001); independent of body mass index and waist/hip ratio, fasting plasma leptin concentration was correlated (n=55) with whole-body glucose disposal (r=-0.27, P<0.04), interventricular septum thickness (r=0.34, P<0.001), posterior wall thickness (r=0.38, P<0.003), and the sum of wall thicknesses (r=0.68, P<0.001). In a multivariate analysis (n=55), age, body mass index, fasting plasma leptin concentration, plasma Na(+) concentration, whole-body glucose disposal, and diastolic blood pressure explained 68% of the variability of the sum of wall thicknesses with fasting plasma leptin concentration (P<0.03), whole body glucose disposal (P<0.002), and diastolic blood pressure (P<0.001), which were significantly and independently associated with the sum of wall thicknesses. In conclusion, our study demonstrates that fasting plasma leptin levels are associated with increased myocardial wall thickness independent of body composition and blood pressure levels in hypertensives.

Topics: Adult; Body Mass Index; Echocardiography; Humans; Hyperinsulinism; Hypertension; Hypertrophy, Left Ventricular; Insulin Resistance; Leptin; Male; Middle Aged

Hepatic steatosis and nonalcoholic steatohepatitis (NASH) have been associated with obesity, non insulin-dependent diabetes mellitus and hyperlipidemia. The present study was designed in order to evaluate whether patients with steatosis/NASH presented common features with the metabolic syndrome.. In 30 patients with nonalcoholic fatty liver the prevalence of hypertension and diabetes; the glucose/insulin profile, lipid profile, and serum leptin were evaluated and correlated with body composition and energy expenditure, assessed by bioimpedance spectroscopy and indirect calorimetry, respectively. Results were compared with a group of eight controls.. Obesity was present in 80% of patients, hypertension in 50% and non insulin dependent diabetes in 33%. Glucose metabolism was altered in 69%, with elevated insulin in 14 patients. Serum leptin, higher in women, was increased in patients: 33.9 +/- 38.9 vs 9.6 +/- 6.9 ng/ml, P< 0.05. There was a correlation between insulin and leptin, both of which correlated with body mass index, fat mass and percentage of body fat. Dyslipidaemia was found in 80% of patients: 45% presented low high density lipoproteins cholesterol, 58% high low density lipoproteins and 38% elevated very low density lipoproteins.. There is a strong association between nonalcoholic fatty liver and features of the metabolic syndrome, suggesting a simultaneous insulin resistance and decreased sensitivity to leptin.

Topics: Adult; Blood Glucose; Body Composition; Calorimetry, Indirect; Case-Control Studies; Diabetes Mellitus, Type 2; Energy Metabolism; Fatty Liver; Female; Humans; Hypertension; Insulin; Leptin; Male; Middle Aged; Obesity; Prevalence; Prospective Studies; Syndrome

The SHROB rat is a unique strain with genetic obesity, hypertriglyceridemia, hyperinsulinemia, renal disease with proteinuria, and genetically determined hypertension, characteristics paralleling human Syndrome X. The obese phenotype results from a single homozygous recessive trait, designated faK, and is allelic with the Zucker fatty trait (fa), but of distinct origin. The faK mutation is a premature stop codon in the extracellular domain of the leptin receptor, resulting in a natural receptor knockout. The SHROB are glucose intolerant compared to heterozygous or wild-type SHR, but retain fasting euglycemia even on a high sucrose diet, suggesting that diabetes requires polygenic interaction with additional modifier genes. Insulin-stimulated phosphorylation of tyrosine residues on the insulin receptor and on the associated docking protein IRS-1 are reduced in skeletal muscle and liver compared to SHR, due mainly to diminished expression of insulin receptor and IRS-1 proteins. Despite multiple metabolic derangements and severe insulin resistance, hypertension is not exacerbated in SHROB compared to SHR. Thus, insulin resistance and hypertension are independent in this model. Increased activity of the sympathetic nervous system may be a common factor leading by separate pathways to hypertension and to insulin resistance. We studied the chronic effects of sympathetic inhibition with moxonidine on glucose metabolism in SHROB. Moxonidine (8 mg/kg/day), a selective I1-imidazoline receptor agonist, not only reduced blood pressure but also ameliorated glucose intolerance. Moxonidine reduced fasting insulin by 47% and plasma free fatty acids by 30%. Moxonidine enhanced expression and insulin-stimulated phosphorylation of IRS-1 in skeletal muscle by 74 and 27%, respectively. Thus, central sympatholytic therapy not only counters hypertension but also insulin resistance, glucose tolerance, and hyperlipidemia in the SHROB model of Syndrome X.

Topics: Animals; Anti-Obesity Agents; Carrier Proteins; Disease Models, Animal; Endocrine System; Female; Hyperinsulinism; Hyperlipidemias; Hypertension; Imidazoles; Insulin Receptor Substrate Proteins; Insulin Resistance; Kidney Diseases; Leptin; Male; Obesity; Phenotype; Phosphoproteins; Phosphorylation; Rats; Rats, Mutant Strains; Receptor, Insulin; Receptors, Cell Surface; Receptors, Leptin

During the last decade several papers were published where obesity in included among the building stones of the so-called metabolic cardiovascular syndrome (along with hypertension, dyslipidaemia, impaired glucose tolerance and hyperinsulinaemia). Several months ago it was also revealed that some patients with the metabolic syndrome suffer from hyperleptinaemia. Leptinaemia is considered by some authors as independent indicator of the risk of accelerated atherosclerosis. The cause of these hypothesis were (in addition to the known conclusions on the occurrence frequent incidence of leptin resistance and insulin resistance) in particular the results of experimental studies where evidence was provided that infusion induced hyperleptinaemia leads in animals to hypertension due to its direct effect on sympathicotonia and peripheral vascular resistance. The authors of these hypothesis assume that hyperleptinaemia (in particular in subjects with metabolic syndrome) in one of the basic causes of hypertension which is frequently encountered in these patients.. To assess the relations between leptinaemia and the blood pressure reading (actual and mean values) and leptinaemia and the classification of hypertension according to WHO.. The authors examined 35 hypertensive subject and 10 subject with tetanies (without hypertension). The blood pressure was assessed under standard conditions (rest, semi-recumbent position, three readings). The mean blood pressure readings during the last three months were obtained from case records. Leptin was assessed by the ELISA method of Bio Vendor Co.. The group of hypertonic can be classified as subjects with mild obesity (BMI 30.1). The values of leptin were elevated but did not differ significantly from those of the normal population. No correlations were found between leptinaemia (incl. values calculated for BMI) and the actual and mean blood pressure readings. No correlations were found between leptinaemia (incl. BP calculated with regard to BMI) and the stage of hypertension according to WHO.. Hypertonic subject do not differ significantly as to the serum leptin concentration from the general population. Leptinaemia does not correlate with the actual or mean blood pressure reading nor with stage of hypertension according to the WHO classification. Thus the authors did not confirm the hypothesis on the fundamental effect of leptinaemia on the genesis and development of hypertension. It is probable that leptin is only one of the many factors which have an impact on blood pressure.

Topics: Blood Pressure; Body Mass Index; Female; Humans; Hypertension; Leptin; Male; Middle Aged

To explore the relationship between serum leptin, hypertension, body mass index (BMI) and energy metabolism.. Serum leptin concentrations were measured by radioimmunoassay. Blood pressure (BMI) blood sugar (Glu), triglycerides (TG), total cholesterol (TC), LDL, HDL, BUN, Cr and Ur were determined in 64 men with essential hypertension (EHT) and 54 male normotensives (NT). The correlation between leptin and other parameters were analyzed.. (1) Serum leptin concentrations n = 118 (3.3 +/- 1.9) micrograms/L in 118 subjects were significantly correlated with SBP, DBP, BMI, Glu, TG, TC and LDL(P < 0.05-P < 0.001). (2) Serum leptin concentrations were strongly correlated with BMI in both EHT and NT groups (P < 0.001). The concentration level was significantly higher in EHT group n = 64 (3.8 +/- 1.9) micrograms/L than in NT group n = 54, (2.8 +/- 1.3) micrograms/L, P < 0.01). The difference in serum leptin concentrations between the two groups disappeared when BMI and age were corrected by analysis of covariance. In NT group, serum leptin concentrations were correlated with SBP (P < 0.05). (3) If the cases of overweight, underweight, hyperglycemia, hyperglyceridemia were excluded, serum leptin concentrations were still highly correlated with BMI, but no longer related to blood pressure.. Serum leptin concentrations are not directly related to blood pressure, but the concentration levels are actually correlated with the degree of obesity and energy metabolism.

Topics: Blood Pressure; Body Mass Index; Energy Metabolism; Humans; Hypertension; Leptin; Logistic Models; Male; Middle Aged

Increased body mass index (BMI) has been correlated with increased blood pressure in human populations. To examine the role of the leptin gene (OB) in essential hypertension in African Americans, we performed affected sib pair analysis on a set of 103 hypertensive African American sibships using four highly polymorphic markers at the human leptin locus. No evidence of linkage was detected between these markers and the phenotype of essential hypertension either in these sibships or in a severely obese subset of 46 sibships in which each sibling had a BMI > or = 85th percentile for the US population. Using BMI rather than hypertension as a quantitative trait, we found significant linkage for the marker D7S504 (P=0.029) but not for the other markers. Significance strengthened in the overweight subset of sibships for this marker (P=0.001), and there was a trend of lower P values for the other three markers. However, multipoint analysis with the use of all four markers simultaneously to estimate linkage between BMI and the leptin locus did not demonstrate a statistically significant relationship. Analysis of the coding region of the leptin gene (exons 2 and 3) by single-strand conformational polymorphism revealed a rare Ile-Val polymorphism at amino acid 45 but revealed no other alterations. These results suggest that the OB gene is not a major contributor to the phenotype of essential hypertension in African Americans, although a minor contribution to the phenotype of extreme obesity in this group cannot be ruled out.

Topics: Adipose Tissue; Adult; Black People; Body Mass Index; Data Interpretation, Statistical; Exons; Female; Genetic Linkage; Genetic Markers; Genotype; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Proteins; Quantitative Trait, Heritable

In this study we wanted to evaluate the relationship between the ob gene product leptin and blood pressure, as well as plasma renin activity and plasma aldosterone levels. We studied 139 subjects with a mean+/-SD age of 50 +/-14 years and a body mass index of 26.5+/-5.3 kg/m2; 110 subjects had essential hypertension and 29 were healthy nonhypertensive controls. Blood pressure was measured in resting conditions in the morning and blood was drawn for the determination of the plasma renin activity, aldosterone, and leptin levels. The mean blood pressure of the population was 155/97 mm Hg. The relationship between these parameters was studied by univariate regression analysis according to gender and, whenever indicated, adjusted for age and body mass. The mean+/-SEM plasma leptin level in the whole population was 9.5+/-0.6 ng/mL (range, 1.1-43.3). Subjects with stage I hypertension had significantly higher plasma leptin levels than normotensive subjects. Systolic blood pressure correlated with the plasma leptin levels and the leptin levels adjusted for body weight in women (r = 0.422, P < .01) and nonhypertensive men (r = 0.644, P = .03) only. Plasma renin activity (r = 0.329, P = .03) and aldosterone levels (r = 0.342, P = .026) correlated with the leptin concentration. A significant relationship between the peripheral expression of the ob gene product leptin and systolic blood pressure was found in women and nonhypertensive men. In view of the multiple functions of leptin a causal relationship is postulated and potential mechanisms may involve modulatory effects of leptin on neuropeptide Y, angiotensinogen gene expression, the modulation of the autonomous nervous system, or effects on the pituitary adrenal axis. Direct relationships between both plasma renin activity and aldosterone levels and leptin support the potential importance of the relationship between leptin and blood pressure. Our observation may be of future importance for the understanding of the link between the increase in blood pressure and increasing body weight.

Topics: Adult; Aged; Angiotensinogen; Blood Pressure; Female; Humans; Hypertension; Leptin; Male; Middle Aged; Obesity; Proteins; Renin

The hemodynamic, hormonal, and renal excretory effects of intravenous bolus administration of synthetic murine leptin were examined in groups of anesthetized normotensive (Sprague-Dawley), hypertensive (spontaneously hypertensive), and both lean and obese Zucker rats. In the normotensive animals (n = 8) an intravenous bolus of 400 microgram/kg of leptin produced a significant six- to sevenfold elevation in sodium excretion compared with controls (n = 8). The onset of natriuresis was delayed for approximately 30-45 min. Mean arterial pressure (MAP), creatinine clearance, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) remained unchanged. In contrast, the hypertensive rats were refractory to the natriuretic effects of leptin when infused either with 400 (n = 8) or 1,600 (n = 8) microgram/kg. Also in these animals MAP, creatinine clearance, PRA, and PAC were unmodified. Finally, whereas lean Zucker rats (n = 8) responded very similarly to the Sprague-Dawley animals, the natriuretic effect of the hormone was attenuated in the obese Zucker groups. At 400 microgram/kg (n = 8) no natriuresis was elicited, but at 1,600 microgram/kg (n = 8) a modest but significant two- to threefold increment in sodium excretion was observed in the obese rats. In both Zucker groups, MAP, creatinine clearance, PRA, and PAC were unchanged. Collectively, these results demonstrate a significant natriuretic effect of exogenous leptin in the normal rat and a blunted saluretic response in hypertension and obesity. It is suggested that leptin may be a potential salt-excretory factor in normal rats and may function pathophysiologically in obesity and hypertension.

Topics: Aldosterone; Animals; Blood Pressure; Hemodynamics; Hypertension; Kidney; Leptin; Male; Obesity; Proteins; Rats; Rats, Sprague-Dawley; Rats, Zucker; Reference Values; Renal Circulation; Renin

The mechanism of the association between obesity and hypertension is not clear. The recently discovered obese gene product, leptin, the levels of which increase in obese subjects, has been shown to reduce food intake and increase sympathetic nervous system activity in animal studies. The present study was undertaken to elucidate the relationship between blood pressure and factors related to obesity, including leptin, in different age groups.. The subjects were 348 Japanese male adolescents (15-17 years old) and 165 men (40-59 years old) not taking medication for hypertension, diabetes mellitus or hyperlipidaemia. Height, weight, blood pressure, heart rate, plasma glucose, lipid profiles, serum insulin and leptin levels were measured in the morning after an overnight fast. Body mass index (BMI), serum leptin level and the homeostasis model insulin resistance index increased in the order of blood-pressure category (i.e. normotensive < high normal < hypertensive) in both the male adolescents and the middle-aged men. In addition, simple linear regressions revealed that both systolic and diastolic blood pressure correlated significantly with serum leptin and the insulin resistance index in both groups. Even after adjustment for age and BMI, the correlation of mean blood pressure with leptin remained in the obese adolescents (r2 = 0.390, P = 0.02). The heart rate also correlated with leptin in the adolescents (r = 0.18, P< 0.001), but not in the middle-aged subjects (r = 0.04). Even after adjustment for age and BMI in adolescents, serum leptin correlated significantly with heart rate.. These results suggest a role for leptin in obesity-related hypertension, especially in adolescents.

Topics: Adolescent; Adult; Age Factors; Animals; Blood Pressure; Body Mass Index; Heart Rate; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Obesity; Proteins

To explore the pathophysiologic roles of the obese (ob) gene product, leptin, in the development of obesity and hypertension, we examined ob gene expression and leptin secretion in obese spontaneously hypertensive rats (obese SHR or Koletsky rats) at the stage of established obesity and hypertension. Expression of the ob gene was augmented in the epididymal, mesenteric, subcutaneous, and retroperitoneal white adipose tissue (WAT) from 20-week-old male obese SHR compared to their lean littermates (lean SHR). Using a radioimmunoassay for rat leptin, we also measured plasma leptin levels in 20-week-old lean and obese SHR. Plasma leptin levels in obese SHR (292.5 +/- 37.1 ng/ml) were more than 100-fold higher than those in lean SHR (2.8 +/- 1.0 ng/ml). The present study demonstrates that ob gene expression and leptin secretion are markedly augmented in obese SHR.

Topics: Animals; Gene Expression; Hypertension; Leptin; Male; Obesity; Proteins; Rats; Rats, Inbred SHR; Rats, Mutant Strains; RNA, Messenger

Insulin resistance, the most important factor in metabolic syndrome X, has been considered to raise blood pressure. Recently it was reported that insulin resistance was related to an elevated plasma level of leptin, which is an adipocyte-specific ob gene product and which plays a role in food intake suppression, thermogenesis, and energy expenditure through the activation of the hypothalamus. However there are no reports that deal with the relationship of insulin resistance to plasma leptin and blood pressure. To evaluate the role of leptin in essential hypertensives, two groups of subjects who were carefully matched for body mass index (BMI) were studied; 22 normotensives (NT, age: 46.5 +/- 2.6 years, BMI: 23.9 +/- 0.4 kg/m2, male/female: 14/8) and 45 mild-to-moderate essential hypertensives (EHT, age: 51.9 +/- 2.0 years, BMI: 24.5 +/- 0.4 kg/m2, male/female: 21/24). We applied the euglycemic hyperinsulinemic glucose clamp technique to all subjects and insulin sensitivity was evaluated as the M value. EHT showed a significantly lower M value (160.2 +/- 7.4 v 184.3 +/- 7.3 mg/m2/min, P < .05) and higher basal plasma immunoreactive leptin level (7.6 +/- 0.8 v 5.0 +/- 0.8 ng/mL, P < .05) than NT, despite the fact that there was no significant difference between NT and EHT in age, gender, or BMI. The relationship between mean blood pressure and leptin showed a significant positive correlation in all of the subjects (r = 0.31, P < .05), suggesting that leptin may be related to a pathophysiology of essential hypertension.

Topics: Adult; Female; Humans; Hypertension; Insulin Resistance; Leptin; Male; Middle Aged; Proteins