leptin and Endocrine-System-Diseases

Anorexia nervosa is a psychiatric disorder characterized by altered body image, persistent food restriction and low body weight, and is associated with global endocrine dysregulation in both adolescent girls and women. Dysfunction of the hypothalamic-pituitary axis includes hypogonadotropic hypogonadism with relative oestrogen and androgen deficiency, growth hormone resistance, hypercortisolaemia, non-thyroidal illness syndrome, hyponatraemia and hypooxytocinaemia. Serum levels of leptin, an anorexigenic adipokine, are suppressed and levels of ghrelin, an orexigenic gut peptide, are elevated in women with anorexia nervosa; however, levels of peptide YY, an anorexigenic gut peptide, are paradoxically elevated. Although most, but not all, of these endocrine disturbances are adaptive to the low energy state of chronic starvation and reverse with treatment of the eating disorder, many contribute to impaired skeletal integrity, as well as neuropsychiatric comorbidities, in individuals with anorexia nervosa. Although 5-15% of patients with anorexia nervosa are men, only limited data exist regarding the endocrine impact of the disease in adolescent boys and men. Further research is needed to understand the endocrine determinants of bone loss and neuropsychiatric comorbidities in anorexia nervosa in both women and men, as well as to formulate optimal treatment strategies.

Topics: Adipokines; Anorexia Nervosa; Disease Management; Endocrine System Diseases; Female; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Leptin; Male; Pituitary-Adrenal System

The prevalence of pediatric obesity in the United States is nearly 17%. Most cases are "exogenous", resulting from excess energy intake relative to energy expenditure over a prolonged period of time. However, some cases of obesity are "endogenous", associated with hormonal, genetic, or syndromic disorders such as hypothyroidism, Cushing's syndrome, growth hormone deficiency, defective leptin signaling, mutations in the melanocortin 4 receptor, and Prader-Willi and Bardet-Biedl syndromes. This article reviews the hormonal, monogenic, and syndromic causes of childhood obesity and identifies critical features that distinguish "endogenous" obesity disorders from the more common exogenous obesity. Findings that raise suspicion for endogenous obesity include onset in infancy, lack of satiety, poor linear growth, dysmorphic features, and cognitive dysfunction. Selection and interpretation of appropriate laboratory tests and indications for subspecialist referral are also discussed.

Topics: Bardet-Biedl Syndrome; Biomarkers; Child; Diagnosis, Differential; Endocrine System Diseases; Genetic Markers; Humans; Infant; Leptin; Mutation; Pediatric Obesity; Prader-Willi Syndrome; Receptor, Melanocortin, Type 4

Adipose tissue is still regarded as a principle site for lipid storage and mobilizing tissue with an important role in the control of energy homeostasis. Additionally, adipose tissue-secreted hormones such as leptin, visfatin, resistin, apelin, omentin, sex steroids, and various growth factors are now regarded as a functional part of the endocrine system. These hormones also play an important role in the immune system. Several in vitro and in vivo studies have suggested the complex role of adipocyte-derived hormones in immune system and inflammation. Adipokines mediate beneficial and detrimental effects in immunity and inflammation. Many of these adipocytokines have a physiological role in metabolism. The uncontrolled secretions of several adipocytokines were associated with the stimulation of inflammatory processes leading to metabolic disorders including obesity, atherosclerosis, insulin resistance and type 2 diabetes. Obesity leads to the dysfunction of adipocytes andcorrelated with the imbalance of adipokines levels. In obese and diabetic conditions, leptin deficiency inhibited the Jak/Stat3/PI3K and insulin pathways. In this review, ample evidence exists to support the recognition of the adipocyte's role in various tissues and pathologies. New integral insights may add dimensions to translate any potential agents into the future clinical armamentarium of chronic endocrine metabolic and inflammatory diseases. Functional balance of both adipocytes and immune cells is important to exert their effects on endocrine metabolic disorders; furthermore, adipose tissue should be renamed not only as a functional part of the endocrine system but also as a new part of the immune system.

Topics: Adipocytes; Adipokines; Adipose Tissue; Endocrine System Diseases; Energy Metabolism; Hormones; Humans; Immunity; Inflammation; Leptin; Nicotinamide Phosphoribosyltransferase; Resistin

Pregnancy is a proinflammatory and hypercoagulable state. Miscarriage concerns approximately 15% of pregnancies. Recurrent miscarriage is a rather rare condition with an estimated incidence of 1% to 3%. However, despite years of investigation, the etiology is not established in up to 50% of cases. A multidisciplinary approach in the evaluation of miscarriage is essential to understand the cause and risk of recurrence. Although genetic factors are the major cause of spontaneous miscarriages, their relationship with recurrent miscarriage is less frequent. Recently, many kinds of genetic polymorphisms have also been found to be associated. Endocrine disorders such as poorly controlled diabetes, polycystic ovary syndrome, and hypothyroidism are linked with recurrent miscarriage. The relationship between recurrent miscarriage and subclinical thyroid disorders and thyroid autoimmunity is disputed, especially in early miscarriages. Uterine malformations should be considered as a cause of recurrent miscarriage. Although autoimmune-based recurrent miscarriage has been described, mainly antiphospholipid antibodies, the role of alloimmune mechanisms remains poorly understood. The influence of congenital thrombophilia is controversial. Antiphospholipid syndrome or antiphospholipid antibody-related recurrent miscarriage, and some endocrinologic disorders, have a specific and effective treatment. Still, the effectiveness of some common treatments needs to be demonstrated.

Topics: Abortion, Habitual; Cell-Derived Microparticles; Chorionic Gonadotropin; Endocrine System Diseases; Female; Glycodelin; Glycoproteins; Humans; Immune System Diseases; Leptin; Polymorphism, Genetic; Pregnancy; Risk Factors; Uterine Diseases; Uterus

Topics: Animals; Anorexia Nervosa; Endocrine System Diseases; Estrogens; Female; Humans; Leptin; Receptors, Estrogen

Women with mood disorders, especially bipolar disorder (BD), have been shown to have high rates of reproductive and metabolic dysfunction. The available data on the functional, anatomic, and clinical neuroendocrine abnormalities in women with BD suggest a two-tiered relationship with mood pathology. First, many of the medications commonly used in the treatment of BD can have deleterious effects on blood levels of reproductive hormones and consequently on the hypothalamic-pituitary-gonadal (HPG) axis and reproductive function. Studies that have specifically addressed the association between psychotropic medications and menstrual abnormalities, polycystic ovary syndrome, and overall reproductive endocrine function in women with BD have found high rates of HPG irregularities in women with BD. Second, there is evidence of reproductive dysfunction in women with BD prior to treatment. In addition, many of the psychotropic medications used in the treatment of BD are associated with weight gain, insulin resistance, and dyslipidemia. These metabolic side effects further compound the neuroendocrine system dysregulation in women with BD. Current understanding of the reproductive and metabolic function in women with BD points to vulnerability, which in turn increases the risk of later-life cardiovascular disease and diabetes, among other morbidities, for women with BD.

Topics: Bipolar Disorder; Dyslipidemias; Endocrine System Diseases; Female; Humans; Hypogonadism; Hypothalamo-Hypophyseal System; Leptin; Lithium Carbonate; Menstruation; Obesity; Pituitary-Adrenal System; Polycystic Ovary Syndrome; Psychotropic Drugs; Valproic Acid

Obesity is associated with several endocrine diseases, including common ones such as hypothyroidism and polycystic ovarian syndrome to rare ones such as Cushing's syndrome, central hypothyroidism and hypothalamic disorders. The mechanisms for the development of obesity vary in according to the endocrine condition. Hypothyroidism is associated with accumulation of hyaluronic acid within various tissues, additional fluid retention due to reduced cardiac output and reduced thermogenesis. The pathophysiology of obesity associated with polycystic ovarian syndrome remains complex as obesity itself may simultaneously be the cause and the effect of the syndrome. Net excess of androgen appears to be pivotal in the development of central obesity. In Cushing's syndrome, an interaction with thyroid and growth hormones plays an important role in addition to an increased adipocyte differentiation and adipogenesis. This review also describes remaining rare cases: hypothalamic obesity due to central hypothyroidism and combined hormone deficiencies.

Topics: Catecholamines; Cushing Syndrome; Endocrine System Diseases; Female; Glucocorticoids; Humans; Hypothalamic Diseases; Hypothyroidism; Leptin; Male; Obesity; Polycystic Ovary Syndrome; Thyroid Function Tests; Triiodothyronine

This review focuses on recent publications concerning medical complications in patients with eating disorders, including anorexia nervosa and bulimia nervosa.. Recent literature continues to reflect that multiple organ systems are frequently affected by eating disorders. The literature underscores the frequently cited risk of premature death in those with anorexia nervosa. A plethora of dermatologic changes have been described, some signaling serious underlying pathophysiology, such as purpura, which indicates a bleeding diathesis. Much of the literature continues to delineate the fact that diabetic patients with eating disorders are at high risk of developing diabetic complications. Gastrointestinal complications can be serious, including gastric dilatation and severe liver dysfunction. Acrocyanosis is common, and patients with anorexia nervosa are at risk of various arrhythmias. Low-weight patients are at high risk for osteopenia/osteoporosis. Nutritional abnormalities are also common, including sodium depletion and hypovolemia, hypophosphatemia and hypomagnesemia. Resting energy expenditure, although very low in low-weight patients, increases dramatically early in refeeding.. Medical complications are common and often serious in patients with eating disorders, particularly those with anorexia nervosa.

Topics: Anorexia Nervosa; Bone Diseases; Bulimia Nervosa; Cardiovascular Diseases; Endocrine System Diseases; Gastrointestinal Diseases; Humans; Leptin; Lung Diseases; Nutrition Disorders; Skin Diseases

Genetic factors are involved in the regulation of body weight and in determining individual responses to environmental factors such as diet and exercise. The identification and characterization of monogenic obesity syndromes have led to an improved understanding of the precise nature of the inherited component of severe obesity and has had undoubted medical benefits, whilst helping to dispel the notion that obesity represents an individual defect in behaviour with no biological basis. For individuals at highest risk of the complications of severe obesity, such findings provide a starting point for providing more rational mechanism-based therapies, as has successfully been achieved for one disorder, congenital leptin deficiency.

Topics: alpha-MSH; Bardet-Biedl Syndrome; Cell Cycle Proteins; Child; Child, Preschool; Endocrine System Diseases; Female; Fibrous Dysplasia, Polyostotic; Fragile X Syndrome; Humans; Leptin; Male; Membrane Proteins; Obesity; Prader-Willi Syndrome; Pro-Opiomelanocortin; Proprotein Convertase 1; Proteins; Receptor, Melanocortin, Type 4; Receptors, Cell Surface; Receptors, Leptin; Syndrome; Vesicular Transport Proteins; WAGR Syndrome

Topics: Abnormalities, Multiple; Child; Drug Resistance; Endocrine System Diseases; Energy Metabolism; Ghrelin; Homeostasis; Hormones; Humans; Hypothalamus, Middle; Insulin; Insulin Resistance; Leptin; Obesity; Peptide Fragments; Peptide Hormones; Peptide YY; Sympathetic Nervous System; Vagus Nerve

Topics: Aldosterone; Calcitriol; Endocrine System Diseases; Erythropoietin; Hormones; Human Growth Hormone; Humans; Kidney Failure, Chronic; Leptin; Parathyroid Hormone

Eating disorders are an important health concern among adolescents. Young women frequently present with signs and symptoms of anorexia nervosa and bulimia nervosa. These disorders represent clinically significant illnesses with serious and sometimes permanent medical complications, including a number of endocrine conditions, that, in general, result from the body s adaptive response to malnutrition. Examples include disorders of metabolism, cortisol and leptin regulation, fluid and electrolyte homeostasis, thyroid function, glucose regulation, growth and development, and reproductive function with the development of amenorrhea as well as the risk of osteoporosis.

Topics: Adolescent; Adult; Amenorrhea; Anorexia Nervosa; Bulimia; Diabetes Mellitus, Type 1; Diagnosis, Differential; Endocrine System Diseases; Feeding and Eating Disorders; Female; Humans; Hydrocortisone; Leptin; Osteoporosis; Thyroid Hormones; Water-Electrolyte Balance

Leptin is a protein that has been identified three years ago, but its role, or at least its deficiency, was suspected from 1950. Dickie and coworkers reported the appearance of a mutant rat in one of their colonies with morbid obesity. The genetic defect was autosomal recessive and was manifested early in life. In December 1994, the gen ob was cloned, which stated the first step for the later identification of the gen product leptin, as a protein of 167 aminoacids expressed in adipose tissue. Since then, leptin has been implicated in many neuroendocrine regulatory pathways. The recent research in leptin roles worth an update review, and so its current and future clinical relevance.

Topics: Animals; Endocrine System Diseases; Growth Hormone; Humans; Hypothalamo-Hypophyseal System; Leptin; Obesity; Pancreas; Reproduction; Thyroid Gland; Thyroid Hormones

Multiple endocrine abnormalities have been reported in stroke patients. In the past few years, it has been claimed that some of these abnormalities may play a role in worsening the neurological deficit and the outcome of stroke. Several mechanisms have been hypothesised, including a direct effect on the development of neuronal cell death, vasospasm, and development of brain edema. In this brief review, we discuss the current knowledge concerning the role of endothelin-1, arginine vasopressin, and cortisol in the pathogenesis of stroke. Finally, we discuss the possibility that leptin, the OB gene product, may be the link of some of these endocrine abnormalities, and that its abnormal secretion during stroke may contribute to the eating disorders and poor nutritional status often seen in these patients.

Topics: Arginine Vasopressin; Brain Ischemia; Endocrine System Diseases; Endothelin-1; Humans; Hydrocortisone; Hypothalamus; Leptin; Pituitary-Adrenal System; Stroke

Topics: Endocrine System Diseases; Female; Humans; Leptin; Male; Obesity; Polycystic Ovary Syndrome; Thyroid Diseases

Molecular genetics will continue to help us to make precise diagnoses. At present, the expertise to achieve this for a specific disease is often exclusive to one unit with a research interest. It will be important to establish a coordinated approach at a supraregional level to provide molecular diagnosis for rare disorders as a fast reliable clinical service. In addition understanding the molecular mechanisms of disease is likely to direct a search for new treatments. For instance, calcium channel blockers have been used in nesidoblastosis to reduce the hypersecretion of insulin, as a result of the recognition of the role that calcium has in the function of the beta-cell ATP sensitive K+ channel. Although the potential benefits of hGH are now being clearly defined in a range of growth disorders, the treatment is invasive and expensive. It is likely that future endocrine therapeutic developments could include slow release growth hormone preparations, orally active growth hormone mimetics, or even hormone production from an ectopic viral cDNA vector. The next "advances in endocrinology" will also reveal whether leptin will have a therapeutic role in appetite control or even the modulation of pubertal development.

Topics: Endocrine System Diseases; Female; Fetal Growth Retardation; Growth Hormone; GTP-Binding Proteins; Humans; Leptin; Pregnancy; Prenatal Exposure Delayed Effects; Proteins

Topics: Adipose Tissue; Animals; Body Weight; Endocrine System Diseases; Homeostasis; Humans; Hypothalamo-Hypophyseal System; Leptin; Neuropeptide Y; Pituitary-Adrenal System; Proteins; Starvation; Wasting Syndrome; Weight Loss

In a brief review of advances in endocrinology in the last two years the author discusses above all the vain expectations of a drug against obesity-the adipose tissue hormone leptin. Its elevated blood level in human obesity indicates that its secretion depends on the mass of adipose tissue and it is not certain whether leptin reduces the food intake in humans. Perhaps resistance to leptin is involved. New receptor diseases were revealed: mutation of LH receptors leads in both sexes to hypogonadism. Mutation of the calcium receptor in parathyroid cells leads to familial hypocalciuric hypercalcaemia or autosomal dominant hypocalcaemia. The complex regulation of the tonus of the vascular wall by endothelins is still the object of interest. Aquaporin is a renal protein which mediates the action of vasopressin. In the sphere of stress evidence is emerging on the participation of CRH in brain activity and the possibility to influence autoimmune inflammations and perhaps even AIDS by interference with the CRH-proopiomelanocortin-ACTH-cortisol system.

Topics: Endocrine System Diseases; Humans; Leptin; Obesity; Proteins

Monogenic non-syndromic obesity is characterized by severe early-onset obesity with abnormal eating behaviour and endocrine disorders. Genes contributing to these rare forms of obesity are mainly located in the leptin/melanocortin pathway, with typically an autosomal additive inheritance of obesity. The normal function of this hypothalamic pathway is essential for the control of energy balance. Genetic variants are involved in 5-30 % of severe early-onset obesity depending on explored populations. Compared to other genes in the pathway especially leptin (LEP), leptin receptor (LEPR), pro-opiomelanocortin (POMC) and prohormone convertase subtilisin/kexin type 1 (PCSK1), Melanocortin 4 receptor (MC4R)-linked obesity is characterized by obesity of variable severity with no notable endocrine phenotypes. Managing patients with monogenic non-syndromic obesity is clinically challenging since they display complex phenotypes and the obesity is often morbid and refractory to classical treatments. Until recent years, there has been a lack of effective and targeted pharmaceutical molecules except for leptin therapy that was available for leptin deficiency. The picture has changed and new promising molecules acting on the leptin-melanocortin pathway such as setmelanotide -a new MC4R agonist- are now emerging as novel targeted therapeutic opportunities.

Topics: Endocrine System Diseases; Humans; Leptin; Mutation; Obesity; Phenotype; Pro-Opiomelanocortin; Receptor, Melanocortin, Type 4; Receptors, Leptin

Endocrine Consequences of Anorexia Nervosa

Topics: Anorexia Nervosa; Endocrine System Diseases; Female; Humans; Leptin; Pituitary Gland; Thyroid Gland

Maternal metabolic syndrome during gestation and lactation leads to several Se-status-related metabolic changes in offspring. MS leads to hepatomegaly, liver oxidation, resistance to insulin challenges and selenoptroteins expression upregulation, producing an energy imbalance in hepatocytes. As Se is necessary for correct heart function, Se deposits are depleted and selenoproteins expression downregulated in heart; this depletion being related to cardiovascular damage. Recently, selenoproteins have been directly implicated in the central endocrine regulation of appetite and energy homeostasis.. To obtain information about how Se is involved in regulating endocrine peripheral energy balance during MS process, two experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65% and Se: 0.1 ppm). At the end of lactation (21d old), the pups' appetite profile, tissular Se deposits and peptides from gastrointestinal tract (including pancreas), leptin, skeletal growth markers and cytokines in serum were measured.. MS-exposed pups present changes in Se homeostasis, appetite profile and endocrine energy balance signals related to impaired insulin secretion and high leptin serum values. This profoundly affects the pups' growth profile since muscle and bones are in catabolic process and brown adipose tissue (BAT) mass decreases.. These results indicate that the pups are suffering a process similar to diabetes type 1 which appeared when dams received low Se dietary supply and they point to Se as an important marker and key treatment for these disorders during gestation and lactation that affect future adult health.

Topics: Animals; Biomarkers; Endocrine System Diseases; Energy Metabolism; Female; Fetal Development; Homeostasis; Insulin Resistance; Leptin; Male; Maternal Nutritional Physiological Phenomena; Metabolic Syndrome; Oxidative Stress; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Wistar; Selenium

Although physical activity is an established risk factor for chronic disease prevention, the specific mechanisms underlying these relationships are poorly understood. We examined the associations between total activity counts and moderate-vigorous physical activity (MVPA) measured by accelerometer, and physical activity energy expenditure measured by doubly labeled water, with plasma levels of proinsulin, insulin, c-peptide, insulin growth factor binding protein-3, insulin growth factor-1, adiponectin, leptin, and leptin-sR.. We conducted a cross-sectional analysis of 526 healthy US women in the Women's Lifestyle Validation Study, 2010 to 2012. We performed multiple linear regression models adjusting for potential lifestyle and health-related confounders to assess the associations between physical activity, measured in quartiles (Q) and biomarkers.. Participants in Q4 versus Q1 of total activity counts had lower proinsulin (-20%), c-peptide (-7%), insulin (-31%), and leptin (-46%) levels, and higher adiponectin (55%), leptin-sR (25%), and insulin growth factor-1 (9.6%) levels (all P trend ≤ 0.05). Participants in Q4 versus Q1 of MVPA had lower proinsulin (-26%), c-peptide (-7%), insulin (-32%), and leptin (-40%) levels, and higher adiponectin (31%) and leptin-sR (22%) levels (all P trend ≤ 0.05). Further adjustment for body mass index (BMI) attenuated these associations, but the associations with adipokines remained significant. Those in Q4 versus Q1 of physical activity energy expenditure had lower leptin (-21%) and higher leptin-sR (10%) levels (all P trend ≤ 0.05), after additional adjustment for BMI. In the sensitivity analysis, the associations were similar but attenuated when physical activity was measured using the subjective physical activity questionnaire.. Our data suggest that greater physical activity is modestly associated with favorable levels of cardiometabolic and endocrine biomarkers, where the strongest associations were found with accelerometer-measured physical activity. These associations may be only partially mediated through BMI, further supporting the role of physical activity in the reduction of cardiometabolic and endocrine disease risk, independent of adiposity.

Topics: Accelerometry; Adiponectin; Aged; Biomarkers; Body Mass Index; C-Peptide; Cardiovascular Diseases; Cross-Sectional Studies; Endocrine System Diseases; Energy Metabolism; Exercise; Female; Humans; Insulin; Insulin-Like Growth Factor Binding Protein 3; Insulin-Like Growth Factor I; Leptin; Middle Aged; Proinsulin; Risk Factors

Endocrine disorders have been shown to be a consequence of blast traumatic brain injury in soldiers returning from military conflicts. Hormone deficiency and adrenocorticotropic hormone (ACTH) dysfunction can lead to symptoms such as fatigue, anxiety, irritability, insomnia, sexual dysfunction, and decreased quality of life. Given these changes following blast exposure, the current study focused on investigating chronic pathology within the hypothalamus following blast, in addition to systemic effects. An established rodent model of blast neurotrauma was used to induce mild blast-induced neurotrauma. Adipose tissue, blood, and brain samples were collected at one and three months following a single blast exposure. Adipose tissue and blood were evaluated for changes in ACTH, adiponectin, C-reactive protein, glial fibrillary acidic protein, interleukin (IL)-1β, and leptin. The hypothalamus was evaluated for injury using immunohistochemical techniques. The results demonstrated that the weight of the blast animals was significantly less, compared with the sham group. The slower rate of increase in their weight was associated with changes in ACTH, IL-1β, and leptin levels. Further, histological analysis indicated elevated levels of cleaved caspase-3 positive cells within the hypothalamus. The data suggest that long-term outcomes of brain injury occurring from blast exposure include dysfunction of the hypothalamus, which leads to compromised hormonal function, elevated biological stress-related hormones, and subsequent adipose tissue remodeling.

Topics: Adiponectin; Adipose Tissue; Adrenocorticotropic Hormone; Animals; Blast Injuries; Body Weight; Brain Injuries; Disease Models, Animal; Endocrine System Diseases; Hypothalamic Diseases; Interleukin-1beta; Leptin; Male; Rats; Rats, Sprague-Dawley

Obesity results from a synergistic relationship between genes and the environment. The phenotypic expression of genetic factors involved in obesity is variable, allowing to distinguish several clinical pictures of obesity. Monogenic obesity is described as rare and severe early-onset obesity with abnormal feeding behavior and endocrine disorders. This is mainly due to autosomal recessive mutations in genes of the leptin-melanocortin pathway which plays a key role in the hypothalamic control of food intake. Melanocortin 4 receptor(MC4R)-linked obesity is characterized by the variable severity of obesity and no notable additional phenotypes. Mutations in the MC4R gene are involved in 2-3% of obese children and adults; the majority of these are heterozygous. Syndromic obesity is associated with mental retardation, dysmorphic features, and organ-specific developmental abnormalities. Additional genes participating in the development of hypothalamus and central nervous system have been regularly identified. But to date, not all involved genes have been identified so far. New diagnostic tools, such as whole-exome sequencing, will probably help to identify other genes. Managing these patients is challenging. Indeed, specific treatments are available only for specific types of monogenic obesity, such as leptin deficiency. Data on bariatric surgery are limited and controversial. New molecules acting on the leptin-melanocortin pathway are currently being developed.

Topics: Adult; Bariatric Surgery; Child; Endocrine System Diseases; Feeding Behavior; Female; Genetic Predisposition to Disease; Humans; Leptin; Mutation; Obesity; Phenotype; Receptor, Melanocortin, Type 4

In rabbits, mean arterial pressure (MAP) increases in response to fat feeding, but does not increase further with progressive weight gain. We documented the progression of adiposity and the alterations in endocrine/cardiovascular function in response to fat feeding in rabbits, to determine whether stabilization of MAP after 3 weeks could be explained by stabilization of neurohormonal factors. Rabbits were fed a control diet or high-fat diet for 9 weeks (n=23). Fat feeding progressively increased body mass and adiposity. Heart rate (HR) was elevated by week 3 (15±3%) but changed little thereafter. The effects of fat feeding on MAP were dependent on baseline MAP and peaked at 3 weeks. From baseline, MAP 80 mm Hg, MAP had increased by 8.1±1.3, 4.7±1.7 and 5.6±1.2 mm Hg, respectively, 3, 6 and 9 weeks after commencing the high-fat diet, but by only 2.6±1.5, 3.0±1.7 and 3.9±1.4 mm Hg, respectively, in control rabbits. Fat feeding did not increase MAP from a baseline >80 mm Hg. Plasma concentrations of leptin and insulin increased during the first 3-6 weeks of fat feeding and then stabilized (increasing by 111±17% and 731±302% by week 9, respectively), coinciding with the pattern of changes in MAP and HR. Plasma total cholesterol, triglycerides, renin activity, aldosterone and atrial natriuretic peptide were not significantly altered by fat feeding. Given that the changes in plasma leptin and insulin mirrored the changes in MAP and HR, leptin and insulin may be important factors in the development of hypertension and tachycardia in the rabbit model of obesity.

Topics: Animals; Blood Glucose; Body Composition; Body Weight; Cardiovascular Diseases; Disease Models, Animal; Endocrine System Diseases; Hemodynamics; Insulin; Leptin; Male; Obesity; Rabbits; Renin-Angiotensin System

Early weaning is associated with changes in the developmental plasticity. Here, we studied the adipocytes morphology, adipokines expression or content in adipose tissue as well as adrenal and thyroid function of neonate and adult offspring primed by early weaning. After birth, lactating rats were divided into 2 groups: EW (early weaning)--dams were wrapped with a bandage to block access to milk during the last 3 days of lactation, and Control--dams whose pups had free access to milk throughout lactation (21 days). At postnatal day (PN) 21, EW pups had lower visceral and subcutaneous adipocyte area (-67.7% and -62%, respectively), body fat mass (-26%), and leptin expression in visceral adipocyte (-64%) but higher leptin expression in subcutaneous adipocyte (2.9-fold increase). Adrenal evaluations were normal, but neonate EW pups presented lower serum T3 (-55%) and TSH (-44%). At PN 180, EW offspring showed higher food intake, higher body fat mass (+21.6%), visceral and subcutaneous adipocyte area (both 3-fold increase), higher leptin (+95%) and ADRβ3 (2-fold increase) content in visceral adipose tissue, and higher adiponectin expression in subcutaneous adipose tissue (+47%) but lower in visceral adipose tissue (-40%). Adult EW offspring presented higher adrenal catecholamine content (+31%), but no changes in serum corticosterone or thyroid status. Thus, early weaning primed for hypothyroidism at weaning, which can be associated with the adipocyte hypertrophy at adulthood. The marked changes in catecholamine adrenal content and visceral adipocyte ADRB3 are generally found in obesity, contributing to the development of other cardiovascular and metabolic disturbances.

Topics: Absorptiometry, Photon; Adiposity; Adrenal Glands; Animals; Animals, Newborn; Disease Models, Animal; Endocrine System Diseases; Gene Expression Regulation; Growth and Development; Intra-Abdominal Fat; Leptin; Obesity; Rats; Rats, Wistar; Receptors, Adrenergic, beta-3; Subcutaneous Fat; Thyroid Function Tests; Weaning

To assess whether endocrine dysfunction may cause derangement in energy homeostasis in patients undergoing hemodialysis (HD), we profiled hormones, during a 3-day period, from the adipose tissue and the gut and the nervous system around the circadian clock in 10 otherwise healthy HD patients and 8 normal controls. The protocol included a 40-h fast. We also measured energy-protein intake and output and assessed appetite and body composition. We found many hormonal abnormalities in HD patients: 1) leptin levels were elevated, due, in part, to increased production, and nocturnal surge in response to daytime feeding, exaggerated. 2) Peptide YY (PYY), an anorexigenic gut hormone, was markedly elevated and displayed an augmented response to feeding. 3) Acylated ghrelin, an orexigenic gut hormone, was lower and did not exhibit the premeal spike as observed in the controls. 4) neuropeptide Y (NPY), a potent orexigenic peptide, was markedly elevated and did not display any circadian variation. 5) Norepinephrine, marginally elevated, did not exhibit the normal nocturnal dip. By contrast, α-melanocyte-stimulating hormone and glucagon-like peptide-1 were not different between the two groups. Despite these hormonal abnormalities, HD patients maintained a good appetite and had normal body lean and fat mass, and there was no evidence of increased energy expenditure or protein catabolism. We explain the hormonal abnormalities as well as the absence of anorexia on suppression of parasympathetic activity (vagus nerve dysfunction), a phenomenon well documented in dialysis patients. Unexpectedly, we noted that the combination of high leptin, PYY, and NPY with suppressed ghrelin may increase arterial blood pressure, impair vasodilatation, and induce cardiac hypertrophy, and thus could predispose to adverse cardiovascular events that are the major causes of morbidity and mortality in the HD population. This is the first report attempting to link hormonal abnormalities associated with energy homeostasis to adverse cardiovascular outcome in the HD patients.

Topics: Adult; Anorexia; Appetite; Body Composition; Cardiovascular Diseases; Circadian Rhythm; Endocrine System Diseases; Energy Metabolism; Fasting; Female; Ghrelin; Homeostasis; Humans; Leptin; Male; Middle Aged; Neuropeptide Y; Norepinephrine; Peptide YY; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency; Risk Factors

The aim of our investigation was the detection of endocrine-metabolic disorders in patients with hyperplastic processes of endomyometrium, uterine cervix and mammary glands. 88 patients of reproductive age with several gynaecological complaints have been investigated. 72 patients with hyperplastic processes in endomyometrium, uterine cervix (hyperplasia, polyposis, myoma) and mammary glands (fibroadenomatosis, adenomatosis) were selected in main group. Control group consisted of 16 patients without any hyperplastic processes of reproductive organs. Metabolic syndrome in main group was revealed in 28% of cases, in control - 18,8% (chi(2)=3,95, p=0,047); insulin resistance - 37,5% and 18,7% (chi(2)=4,59, p=0,033), respectively; obesity - 52,8% and 25,0% (chi(2)=4,05, p=0,045), respectively; dyslipidemia - 52,8% and 0,0%; hypertension - 26,4% and 12,5% (chi(2)=1,88, p=NS), respectively. Blood leptin level in main group was - 13,7+/-10,9 ng/ml, and in control - 5,0+/-2,9 ng/ml (p=0,005). Our results suggest that metabolic syndrome and its components significantly influences the formation of hyperplastic processes of endomyometrium, uterine cervix and mammary glands. Blood leptin level is significantly increased in patients with hyperplastic pathologies.

Topics: Adult; Breast Neoplasms; Cervix Uteri; Endocrine System Diseases; Female; Humans; Hyperplasia; Leptin; Mammary Glands, Human; Metabolic Syndrome; Reproduction; Uterine Cervical Neoplasms

A carboxypeptidase E (CPE) knockout (KO) mouse was generated by deletion of exons 4 and 5 from the CPE gene, and its phenotype was characterized. KO mice became obese by 10-12 wk of age and reached 60-80 g by 40 wk. At this age, body fat content was more than double that in the wild-type (WT) controls. The null animals consumed more food overall, were less physically active during the light phase of the light-dark cycle, and burned fewer calories as fat than WT littermates. Fasting levels of glucose and insulin-like immunoreactivity in plasma were elevated in both male and female KO mice at approximately 20 wk; males recovered fully and females partially from this state by 32 wk. At this time, insulin-like immunoreactivity in the plasma, identified as proinsulin, was 50-100 times higher than that of the WT animals. The KO mice showed impaired glucose clearance and were insulin resistant. High levels of leptin and no circulating fully processed cocaine- and amphetamine-related transcript, a peptide that is responsive to leptin-induced feedback inhibition of feeding, were found in serum. The KO mice were subfertile and showed deficits in GnRH processing in the hypothalamus. Behavioral analyses revealed that KO animals showed diminished reactivity to stimuli and had reduced muscle strength and coordination, as well as visual placing and toe-pinch reflexes. These data demonstrate that CPE KO mice display a wide range of neural and endocrine abnormalities and suggest that CPE may have additional physiological roles beyond those ascribed to peptide processing and sorting of prohormones in cells.

Topics: Adipose Tissue; Animals; Behavior, Animal; Body Size; Body Weight; Calorimetry, Indirect; Carboxypeptidase H; Chromatography, High Pressure Liquid; Drinking; Eating; Endocrine System Diseases; Female; Fertility; Glucose Intolerance; Insulin Resistance; Leptin; Male; Mice; Mice, Knockout; Nerve Tissue Proteins; Obesity; Phenotype; Proinsulin

We have previously demonstrated that genetically based leptin deficiency due to a missense leptin gene mutation in a highly consanguineous extended Turkish pedigree is associated with morbid obesity and hypogonadism. We have now performed detailed assessments of endocrine, sympathetic, and immune function. We have also identified a new adult female homozygous patient in this extended family who is severely obese and amenorrheic. In this family all wild-type and heterozgous individuals have normal body weight. Seven obese members of this family, whom we presume to have been leptin deficient, died during childhood. There are several findings that indicate potentially novel targets for leptin action in humans. Four homozygous patients (1 adult male, 2 adult females, and 1 child) have sympathetic system dysfunction, whereas all heterozygous subjects have normal sympathetic system function. Despite sympathetic system dysfunction and postural hypotension, 1 of 3 homozygous adult patients has impaired renin-aldosterone function. The patients also exhibit alterations in GH and PTH-calcium function, and 1 of them has decreased bone mineral density. Despite their obesity, these patients do not have risk factors for cardiovascular disease, such as hypertension, impairments in lipid metabolism, or hyperleptinemia [corrected]. These data support the hypothesis that the obese may have central, but not peripheral, resistance to the effects of leptin and that hyperleptinemia [corrected] may mediate the cardiovascular morbidity of the obese who are not leptin deficient. Furthermore, these data indicate that there may be several new targets for leptin action in human physiology. Such new targets may lead to novel pharmacological strategies for the use of leptin agonists and antagonists in the treatment of human disease. All 19 normal weight individuals in this family are alive, whereas 7 of 11 obese individuals died in childhood after infections. The odds ratio for mortality in the context of this obesity phenotype is 25.4, indicating that this mutation severely impairs key biological functions during childhood, negatively impacting on survival. We found that only the obese child in this family had thyroid function abnormalities. The oldest homozygous female patient started to menstruate, albeit with a luteal phase defect, 7 months ago, after a delay of over 20 yr, whereas the younger adult subjects are still hypogonadic. Thus, we conclude that due to their long life span,

Topics: Adult; Aged; Child; Endocrine System Diseases; Female; Humans; Immune System; Leptin; Male; Middle Aged; Mutation, Missense; Pedigree; Sympathetic Nervous System; Vascular Resistance