leptin and Stroke

Ischemic stroke is the fifth leading cause of death in the USA and is the leading cause of serious, long-term disability worldwide. The principle sex hormones (estrogen, progesterone, and testosterone), both endogenous and exogenous, have profound effects on various stroke outcomes and have become the focus of a number of studies evaluating risk factors and treatment options for ischemic stroke. In addition, the expression of other hormones that may influence stroke outcome, including select adipose-derived hormones (adiponectin, leptin, and ghrelin), can be regulated by sex hormones and are also the focus of several ischemic stroke studies. This review aims to summarize some of the preclinical and clinical studies investigating the principle sex hormones, as well as select adipose-derived hormones, as risk factors or potential treatments for ischemic stroke. In addition, the potential for relaxin, a lesser studied sex hormone, as a novel treatment option for ischemic stroke is explored.

Topics: Adiponectin; Animals; Brain Ischemia; Ghrelin; Gonadal Steroid Hormones; Humans; Leptin; Relaxin; Stroke

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

Stroke is a multifactorial disease contributing to significant noncommunicable disease burden in developing countries. Risk of stroke is largely a consequence of morbidities of diabetes, obesity, hypertension, and heart diseases. Incidence of stroke is directly proportional to body mass index. Adipose tissue stores energy as well as acts as an active endocrine organ, which secretes numerous humoral factors. Adiponectin and leptin are the commonest adipocytokines and have been invariably linked to the development of coronary heart disease and may be involved in the underlying biological mechanism of stroke. Leptin and adiponectin mediate proatherogenic and antiatherogenic responses, respectively, and hence, determining the plasma or serum levels of leptin and adiponectin alone or in combination may act as a novel prognostic biomarker for inflammation and atherosclerosis in stroke. This review addresses leptin- and adiponectin-mediated inflammatory mechanism in ischemic stroke and their potential as therapeutic targets.

Topics: Adiponectin; Animals; Humans; Inflammation; Ischemia; Leptin; Obesity; Stroke

Although high leptin concentration has been shown to be correlated with established vascular risk factors, epidemiologic studies have reported inconclusive results on the association between leptin and cardiovascular diseases (CVD). Therefore, a meta-analysis was performed to evaluate this issue.. We searched Pubmed, Embase, and the Cochrane Library from their inception to Jan 2016 for both case-control and cohort studies that assessed leptin concentration and CVD risk. Reports with odds ratio (OR), risk ratio (RR) and corresponding 95% confidence intervals (CI) were considered. The data were extracted by two investigators independently.. A total of 13 epidemiologic studies totaling 4257 CVD patients and 26710 controls were included. A significant inverse association was shown between leptin and coronary heart disease (CHD), with an overall OR of 1.16 (95% CI: 1.02-1.32), but not for stroke (OR = 1.21, 95% CI 0.98-1.48) under sociodemographic adjustment. Further adjustment for additional cardiovascular risk factors resulted in ORs of 1.16 (95% CI 0.97-1.40) for CHD and 1.10 (95% CI 0.89-1.35) for stroke. The findings remained when analyses were restricted to high-quality studies and indicated OR estimates of 1.07 (95% CI 0.96-1.19) for CHD and 0.98 (95% CI 0.76-1.25) for stroke. In a subgroup meta-analysis, a high leptin level was not independently associated with CHD in both females (OR = 1.03, 95% CI 0.86-1.23) and males (OR = 1.09, 95% CI 0.95-1.26) or with stroke in both females (OR = 1.13, 95% CI 0.87-1.47) and males (OR = 0.80, 95% CI 0.59-1.09). There was no significant publication bias as suggested by Egger test outcomes.. Our findings indicate that high leptin levels may not be associated with risks of CHD and stroke. Further large, well-designed prospective cohort studies are needed to fully evaluate the role of leptin on the risk of CVD.

Topics: Coronary Disease; Humans; Leptin; Risk Factors; Stroke

This meta-analysis aimed to investigate the association of leptin levels with pathogenetic risk of CHD and stroke.. Studies were identified in the PubMed, Embase, and Springer link database without language restriction. Odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs) were used as effect indexes. The association of leptin levels with pathogenetic risk of CHD and stroke, as well as the risk variation of CHD with each additional one unit of leptin level were examined via meta-analysis. The publication bias was assessed via Egger's linear regression test.. Eight nested case-control studies consisting of 1,980 patients and 11,567 controls were included for current meta-analysis. ORs (95% CIs) of association of leptin levels with CHD and stroke was 1.90 (1.06, 3.43), and 2.14 (1.48, 3.08), respectively. In addition, significant result was obtained regarding the risk variation of CHD with each additional one unit of leptin level (OR =1.04, 95% CI =1.00-1.08, P=0.044). There was no significant publication bias as suggested by Egger test outcomes.. There was a significant association of leptin with pathogenetic risk of CHD and stroke, and raised leptin levels could significantly increase the pathogenetic risk of CHD.

Topics: Biomarkers; Case-Control Studies; Coronary Artery Disease; Genetic Predisposition to Disease; Humans; Leptin; Odds Ratio; Risk; Stroke

Convincing evidence has accumulated of regulation of bone by the central nervous system. The neural connection between brain and bone is mediated centrally by classic neurotransmitters and several neuropeptides, and peripherally by many of the same neurotransmitters and neuropeptides, albeit with actions opposite to their central effects. Pharmacologic blockade of ß2-adrenergic receptors or disruption of the gene encoding them increases bone mass, whereas increased activity of the sympathetic nervous system (SNS) contributes to bone loss. Brainstem serotonergic neurons regulate SNS activity and its modulation by leptin. Physiologic stimulation of osteoblastic nicotinic receptors results in proliferation and deposition of bone, whereas higher levels inhibit osteoblast function. Activation of sensory nerves has a centrally mediated action on bone, albeit poorly understood. The relative importance of, and interactions between autonomic, sensory, and peripheral nervous system actions on bone mass are also not clear in healthy individuals, and less so in pathologic states.

Topics: Acetylcholine; Animals; Bone Remodeling; Calcitonin Gene-Related Peptide; Humans; Hypothalamus; Leptin; Neuropeptides; Norepinephrine; Osteoporosis; Parasympathetic Nervous System; Primary Dysautonomias; Stroke; 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

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

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

Leptin is an adipose tissue-derived hormone associated with cardiovascular risk factors. We examined whether leptin predicts major adverse cardiac events (MACE) in coronary artery disease (CAD) patients.. Fasting plasma leptin levels were measured in 1327 male and 619 female CAD patients. The patients were followed up for two years. The primary endpoint (MACE) was the composite of a hospitalisation for congestive heart failure (CHF) or a cardiac death. The secondary endpoint was the composite of an acute coronary syndrome (ACS) or a stroke.. In regression analysis including established risk variables, high leptin levels were associated with a significantly increased risk of MACE (HR 3.37; 95%CI 1.64-6.90; p = 0.001) and ACS or stroke (HR 1.95; 95%CI 1.29-2.96; p = 0.002). Adding leptin to the risk model for MACE increased the C-index from 0.78 (95%CI 0.71-0.85) to 0.81 (0.74-0.88) and improved classification (NRI 0.36; 95%CI 0.13-0.60; p = 0.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001-0.030; p = 0.031).. High plasma leptin levels predict short-term occurrence of CHF or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible harmful effects of leptin should be thoroughly investigated. Key messages Leptin is a peptide hormone secreted mainly by adipose tissue. It has been associated with several cardiovascular risk factors. High leptin levels predict the short-term occurrence of congestive heart failure or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible detrimental effects of leptin on the cardiovascular system should be thoroughly investigated.

Topics: Acute Coronary Syndrome; Aged; Biomarkers; Coronary Artery Disease; Death, Sudden, Cardiac; Fasting; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Leptin; Male; Middle Aged; Predictive Value of Tests; Risk Assessment; Risk Factors; Stroke

To investigate the relationships between plasma leptin and adiponectin levels and recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes.. A nested case-control study examined circulating leptin and adiponectin levels in plasma obtained 4-6 years after entry into the Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) trial. Plasma was assayed from 184 men who suffered recurrent events within 4.4 years after blood collection and 184 matched controls who remained free of further events. The association between cardiovascular events and the explanatory variables was examined by conditional logistic regression analysis.. Relative risk (RR) increased across increasing leptin quartiles; the highest quartile compared with the lowest quartile was related to the highest risk (P for trend=0.002); the increased risk remained after adjustment for risk factors (P=0.018) or for obesity (P=0.038), but in the final model (adjusted for randomized treatment, other drugs, LIPID risk score, age and body mass index), the risk was attenuated (RR=1.61, 95% CI: 0.72-3.57, P for trend=0.34). Adiponectin did not predict cardiovascular events. Subjects randomly allocated to pravastatin had 6% lower leptin levels (P=0.04) than those allocated to placebo.. Plasma leptin was a significant and independent predictor of recurrent cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) in men with earlier acute coronary syndromes.

Topics: Adiponectin; Aged; Biomarkers; Cardiovascular Diseases; Case-Control Studies; Coronary Disease; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Leptin; Logistic Models; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Pravastatin; Recurrence; Risk; Stroke

This research aimed to combine serum NLR-pyrin domain containing 1 (NLRP1) levels and collateral circulation to assess ischemic stroke patients and predict the prognoses of the patients. This present prospective observational study enrolled 196 ischemic stroke patients. All patients underwent CTA as well as digital subtraction angiography (DSA) to assess collateral circulation by American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR). In addition, we collected serum samples from 100 patients with carotid atherosclerosis as controls. The serum NLRP1, tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-1β and C-reactive protein (CRP) levels were measured by enzyme-linked immunosorbent assay (ELISA). The age, BMI, sex, smoke condition, diastolic blood pressure, systolic blood pressure, National Institutes of Health Stroke Scores (NIHSS), modified Rankin Scale (mRS) scores, imaging indicators and the levels of triglyceride, total cholesterol (TC), low-density leptin cholesterol (LDLC), high-density leptin cholesterol of all subjects were recorded. All data used SPSS 18.0 to statistical analyses. The serum levels of NLRP1 were remarkably enhanced in the ischemic stroke patients compared with the carotid atherosclerosis patients. The NIHSS score, the mRS score after 90 days and the levels of NLRP1, CRP, TNF-α IL-6 and IL-1β of ischemic stroke patients in the ASITN/SIR grade 0 to 2 group were remarkably elevated than the ischemic stroke patients in ASITN/SIR grade 3 to 4 group. Spearman analysis supported that a positive correlation existed among the NLRP1, CRP, IL-6, TNF-α, and IL-1β levels. The NIHSS score, infarct volume and the levels of NLRP1, IL-6, TNF-α, and IL-1β of ischemic stroke patients in the mRS score ≥ 3 group were remarkably elevated than the ischemic stroke patients in the mRS score ≤ 2 group. ASITN/SIR grade and NLRP1 could be potential diagnostic biomarkers of poor prognosis of ischemic stroke patients. It was found that NLRP1, ASITN/SIR grade, infarct volume, NIHSS, IL-6, and IL-1β were the risk factors for bad prognosis of ischemic stroke patients. This study showed that the serum NLRP1 levels were remarkably decreased in ischemic stroke patients. In addition, the serum NLRP1 levels and ASITN/SIR grade could predict the prognosis of ischemic stroke patients.

Topics: Brain Ischemia; Carotid Artery Diseases; Cholesterol; Clinical Relevance; Collateral Circulation; Computed Tomography Angiography; Humans; Infarction; Interleukin-6; Ischemic Stroke; Leptin; NLR Proteins; Stroke; Tumor Necrosis Factor-alpha

Atherosclerosis is the main cause for most cardiovascular diseases, and new biomarkers for this condition are always needed. Peptidase M20 domain containing 1 (PM20D1) is associated with both lipid metabolism and obesity. However, no study focuses on the role of PM20D1 in carotid atherosclerosis.. The present study aimed to investigate the role of PM20D1 in carotid atherosclerosis patients.. The present prospective observational study contained a total of 231 carotid atherosclerosis patients, who went to our department between July 2018 and December 2019. Blood samples and medical characteristics were also obtained from 231 healthy individuals with the same body mass index distribution of carotid atherosclerosis patients. Serum PM20D1 was determined using enzyme-linked immunosorbent assay. Clinical and demographic characteristics of all patients were collected, including age, sex, body mass index and medical history. Levels of C-reactive protein, tumor necrosis factor, homocysteine, as well as total cholesterol, triglyceride, high-density leptin cholesterol and low-density leptin cholesterol were recorded. Statistical analysis was conducted using the SPSS software, with p<0.05 as statistically different.. Serum PM20D1 levels were markedly lower in carotid atherosclerosis patients when compared to the healthy control, which were significantly lower in severe carotid atherosclerosis patients and carotid atherosclerosis/stroke patients. Patients with unstable plaques showed markedly lower PM20D1 when compared to patients with stable plaques. No significant difference was found among carotid atherosclerosis patients with different body mass index. Patients with higher PM20D1 levels showed significantly lower expression of C-reactive protein, tumor necrosis factor, homocysteine, triglyceride, total cholesterol and low-density leptin cholesterol. PM20D1 was negatively correlated with C-reactive protein, tumor necrosis factor, homocysteine, total cholesterol and low-density leptin cholesterol in carotid atherosclerosis patients, and could be used as a biomarker for severe carotid atherosclerosis patients or carotid atherosclerosis patients with stroke. Sex, tumor necrosis factor, homocysteine and PM20D1 were risk factors for carotid atherosclerosis.. PM20D1 was decreased in carotid atherosclerosis patients and was associated with severity, plaque stability, and levels of C-reactive protein, tumor necrosis factor, homocysteine, triglyceride, total cholesterol and low-density leptin cholesterol in carotid atherosclerosis patients.. A aterosclerose é a principal causa da maioria das doenças cardiovasculares, e novos biomarcadores para essa condição são sempre necessários. O domínio da peptidase M20 contendo 1 (PM20D1) está associado ao metabolismo lipídico e à obesidade. No entanto, nenhum estudo se concentra no papel do PM20D1 na aterosclerose carotídea.. O objetivo deste estudo foi investigar o papel do PM20D1 em pacientes com aterosclerose carotídea.. Estudo observacional prospectivo conduzido com um total de 231 pacientes com aterosclerose carotídea que estiveram em nosso departamento entre julho de 2018 e dezembro de 2019. Amostras de sangue e dados médicas foram obtidos de outros 231 indivíduos saudáveis com o mesmo índice de massa corporal (IMC) dos pacientes com aterosclerose carotídea. O PM20D1 sérico foi determinado por ensaio imunossorvente ligado a enzima (ELISA). As características clínicas e demográficas de todos os pacientes foram listadas, incluindo idade, sexo biológico, IMC e histórico médico. Os níveis de proteína C reativa (PCR), fator de necrose tumoral, homocisteína, colesterol total, triglicerídeos, leptina-colesterol de alta densidade e leptina-colesterol de baixa densidade foram registrados. Realizou-se análise estatística no software SPSS, com p<0,05 considerado estatisticamente significante.. Os níveis séricos de PM20D1 foram marcadamente mais baixos em pacientes com aterosclerose carotídea comparados aos controles saudáveis, sendo significativamente mais baixos em pacientes com aterosclerose carotídea grave e pacientes com aterosclerose carotídea/acidente vascular cerebral. Pacientes com placas instáveis apresentaram PM20D1 marcadamente menor quando comparados a pacientes com placas estáveis. Nenhuma diferença significativa foi encontrada entre pacientes com aterosclerose carotídea com diferentes IMC. Pacientes com níveis mais elevados de PM20D1 apresentaram expressão significativamente menor de PCR, fator de necrose tumoral, homocisteína, triglicerídeos, colesterol total e colesterol de baixa densidade. PM20D1 correlacionou-se negativamente com PCR, fator de necrose tumoral, homocisteína, colesterol total e leptina de baixa densidade em pacientes com aterosclerose carotídea, podendo ser usado como biomarcador para pacientes com aterosclerose carotídea grave ou com aterosclerose carotídea e acidente vascular cerebral. Sexo biológico, fator de necrose tumoral, homocisteína e PM20D1 foram considerados fatores de risco para aterosclerose carotídea.. O PM20D1 estava diminuído em pacientes com aterosclerose carotídea e foi associado com gravidade, estabilidade da placa, níveis de PCR, fator de necrose tumoral, homocisteína, triglicerídeos, colesterol total e colesterol de baixa densidade em pacientes com aterosclerose carotídea.

Topics: Amidohydrolases; Biomarkers; C-Reactive Protein; Carotid Artery Diseases; Cholesterol; Homocysteine; Humans; Leptin; Peptide Hydrolases; Plaque, Atherosclerotic; Risk Factors; Stroke; Triglycerides; Tumor Necrosis Factors

Oral anticoagulation is effective for stroke prevention in atrial fibrillation (AF). However, strokes may still occur in high-risk individuals. We conducted a prospective trial to assess the association between adipocytokine serum levels and surrogate parameters for thromboembolic events.. Our results suggest that adiponectin and resistin may act as potential biomarkers to identify individuals with AF who are at high thromboembolic risk.

Topics: Adipokines; Adiponectin; Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Biomarkers; Body Mass Index; Cross-Sectional Studies; Cytokines; Echocardiography, Transesophageal; Female; Germany; Humans; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Prospective Studies; Resistin; Risk Assessment; Risk Factors; Stroke; Thromboembolism; Thrombosis; Time Factors; Treatment Outcome

Neuroprotective effects of leptin have been shown in mouse model of cerebral ischemia/reperfusion injury and primary cortical neuronal culture with oxygen-glucose deprivation (OGD), while the underlying mechanisms are less understood. In the present study, we investigated whether leptin modulated mitochondrial function through JAK2/STAT3 in vivo mouse model of transient middle cerebral artery occlusion (MCAO) and in OGD-challenged primary neuronal cultures. JAK2/STAT3; mitochondrial biogenesis markers (PGC-1α); and apoptosis-associated proteins (caspase-3, BCL-2, BCL-XL, and cytochrome c) were detected by western blotting and reverse transcription-polymerase chain reaction at 1 h before and after ischemia/reperfusion. P-STAT3 and PGC-1α in neurons and astrocytes were detected. Moreover, mitochondrial morphology of the ischemic ipsilateral penumbra is examined using transmission electron microscopy. Primary cerebral cortical neurons were evaluated for viability, mitochondrial membrane potential (MMP), and apoptosis to assess whether dose-dependent neuroprotective effects of leptin during OGD were mitigated by the JAK2/STAT3 inhibitor AG490. Leptin activated JAK2/STAT3 signaling in neurons and astrocytes distributed in the ischemic ipsilateral penumbra, with peak p-STAT3 levels observed at 1 h after reperfusion. Leptin increased PGC-1α, BCL-2, and BCL-XL protein levels, cell viability, and MMP and decreased apoptosis both in vitro and in vivo; these effects were reversed by AG490 treatment. Our findings suggest that leptin-mediated neuroprotective effects in tMCAO may peak at 1 h to induce the transcription of its target gene PGC-1α, stabilization of MMP, inhibition of mitochondrial permeability transition pore opening, release of cytochrome c, and apoptosis.

Topics: Animals; Apoptosis; Brain; Brain Ischemia; Infarction, Middle Cerebral Artery; Janus Kinase 2; Leptin; Male; Membrane Potential, Mitochondrial; Mice; Mice, Inbred C57BL; Mitochondria; Neurons; Neuroprotective Agents; Proto-Oncogene Proteins c-bcl-2; Reperfusion Injury; Signal Transduction; STAT3 Transcription Factor; Stroke; Transcription Factors

Leptin may be associated with cardiovascular disease. We tested to determine whether leptin is a marker for first-ever acute ischemic stroke (AIS) in a nested case-referent study.. Consecutive patients with first-ever AIS from May 2017 to December 2017 were included. Referents were matched for sex, age and body mass index. Serum leptin levels and routine tests were examined in both groups.. The median serum level of leptin in the stroke patients was 14.3 (interquartile range [IQR], 7.2-21.7) ng/ml, which was significantly higher (P < 0.001) than in the referents (10.7; 5.7-13.6 ng/ml). There was a positive correlation between serum level of leptin and National Institute of Health Stroke Scale score (r[Spearman] = 0.43, P < 0.001). In addition, serum leptin levels paralleled lesion size. Median serum level of leptin in patients with small lesions, medium lesions and large lesions was 7.3 (IQR, 5.3-14.3) ng/ml, 13.9 (IQR, 7.0-21.3) ng/ml, 20.5 (IQR, 12.4-32.7) ng/ml, respectively (analysis of variance: P < 0.001). In the univariate model matching for sex and age, leptin as a continuous variable was associated with AIS, after adjustment for possible confounders (odds ratio [OR] 1.07, 95% confidence interval [CI]: 1.04-1.11; P < 0.001). After adjusting for all other factors, leptin remained an independent stroke predictor with an adjusted OR of 1.03 (95% CI, 1.00-1.10; P = 0.006). Interestingly, the association between AIS and leptin level was more pronounced among men (adjusted OR = 1.05, 95% CI: 1.01-1.12; P < 0.001) when compared with women (adjusted OR = 1.03, 95% CI: 1.10-1.11; P = 0.009).. Serum leptin is associated with first-ever AIS, lesion size and stroke severity in a Chinese cohort.

Topics: Aged; Biomarkers; Brain Ischemia; China; Female; Humans; Leptin; Male; Middle Aged; Severity of Illness Index; Stroke

Topics: Adiponectin; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Brain Ischemia; Cytokines; Female; Humans; Intracranial Hemorrhages; Leptin; Male; Middle Aged; Nicotinamide Phosphoribosyltransferase; Stroke; Treatment Outcome

The role of adiponectin, leptin, and resistin and the -420C>G polymorphism of the resistin gene promoter in the pathogenesis of ischemic stroke are controversial. We aimed to evaluate whether serum levels of these adipokines and the -420C>G polymorphism are associated with ischemic stroke severity and in-hospital outcome.. We prospectively studied 93 patients who were consecutively hospitalized for acute ischemic stroke (39.8% males, age 79.7 ± 6.3 years). Stroke severity was evaluated at admission by the National Institutes of Health Stroke Scale (NIHSS). In-hospital outcome was evaluated by dependency rates at discharge and in-hospital mortality.. The G allele was more prevalent in patients with severe stroke (P < .05). Independent predictors of severe stroke were high-sensitivity C-reactive protein levels (relative risk [RR] 1.43, 95% confidence interval [CI] 1.08-1.91, P < .05). Patients with dependency at discharge had lower serum leptin levels (P < .05). Independent predictors of functional dependence were prior ischemic stroke (RR 7.55, 95% CI 1.69-33.58, P < .01), serum triglyceride levels (RR .98, 95% CI .96-0.99, P < .05), and NIHSS at admission (RR 1.47, 95% CI 1.17-1.84, P < .001). The G allele was more prevalent in patients who died (P < .05). Independent predictors of in-hospital mortality were systolic blood pressure (RR 1.09, 95% CI 1.01-1.19, P < .05) and NIHSS at admission (RR 1.26, 95% CI 1.08-1.48, P < .005).. The G allele of the -420C>G polymorphism of the resistin gene promoter appears to be associated with more severe stroke and higher in-hospital mortality in patients with acute ischemic stroke. Higher leptin levels appear to be related to favorable functional outcome.

Topics: Adiponectin; Aged; Aged, 80 and over; Brain Ischemia; Chi-Square Distribution; Disability Evaluation; Female; Gene Frequency; Genetic Predisposition to Disease; Hospital Mortality; Hospitalization; Humans; Leptin; Logistic Models; Male; Odds Ratio; Phenotype; Polymorphism, Genetic; Promoter Regions, Genetic; Prospective Studies; Recovery of Function; Resistin; Risk Factors; Severity of Illness Index; Stroke; Time Factors; Treatment Outcome

Leptin is a major adipokine that regulates weight balance and energy homeostasis. There is inconsistent evidence linking circulating leptin levels to risk of stroke. We tested the hypothesis that leptin levels are associated with risk of incident stroke in an elderly community based sample.. Serum leptin levels were assayed in 757 stroke free individuals (mean age, 79 years; 62% women) from the Framingham Original Cohort at the 22nd examination cycle (1990-1994). Incidence of all -stroke and ischemic stroke were prospectively ascertained.. During a mean follow up of 10 years, 119 individuals developed stroke (99 ischemic strokes). In multivariable Cox regression models, log leptin levels were not associated with incidence of all -stroke or ischemic stroke (hazard ratios per SD increment in log leptin 0.90 [0.73-1.09] and 0.89 [0.72-1.11], respectively). The results were suggestive for potential effect modification by waist/hip ratio for the association between leptin and stroke (P=0.03). Adjusting for age, sex, and established stroke risk factors, analysis stratified by waist/hip ratio quartiles revealed a lower incidence of first-ever all-stroke and ischemic stroke associated with higher leptin levels among only subjects in the top waist/hip ratio quartile (hazard ratio, 0.64 [0.43, 0.95] versus 0.98 [0.77, 1.25] for incident all-stroke and 0.61 [0.39, 0.95] versus 0.96 [0.74, 1.26] for ischemic stroke).. Leptin levels were not directly related to the risk of incident stroke overall but there was an inverse association with stroke in the top waist/hip ratio quartile. Further investigations are required to confirm these findings and explore possible mechanisms for the observed association.

Topics: Aged; Aged, 80 and over; Biomarkers; Brain Ischemia; Cohort Studies; Female; Humans; Incidence; Leptin; Longitudinal Studies; Male; Proportional Hazards Models; Prospective Studies; Radioimmunoassay; Risk Factors; Stroke; Waist-Hip Ratio

Different adipokines have been associated with atherosclerotic plaque rupture and cardiovascular events, such as acute ischaemic stroke (AIS). However, the potential role of these molecules in postischaemic brain injury remains largely unknown.. We performed a substudy analysis on nonobese patients with first atherothrombotic stroke (n = 35) from a recently published prospective cohort. Primary endpoint was to investigate the predictive value of serum leptin/adiponectin ratio on neurological recovery at 90 days after AIS. The secondary endpoint was the predictive value of serum adipokine levels of clinical and radiological outcomes at a shorter follow-up (at days 1 and 7 after AIS). The radiological evaluation included ischaemic lesion volume and haemorrhagic transformation (HT). The clinical examination was based on National Institutes of Health Stroke Scale (NIHSS) and modified Rankin Scale (mRS).. At day 1 after AIS, serum leptin and leptin/adiponectin ratio were increased and inversely correlated with both radiological and clinical parameters at all follow-up time points. Once identified the best cut-off points by receiver operating characteristic (ROC) analysis, risk analysis showed that higher circulating leptin improved neurological recovery at day 90. In addition, leptin/adiponectin ratio maintained statistical significance after adjustment for age, gender and thrombolysis, also predicting the occurrence of HT in the first 7 days after AIS (adjusted OR 0·15 [95% CI 0·03-0·83); P = 0·030]).. Higher leptin/adiponectin ratio at day 1 predicted better neurological outcomes in patients with atherothrombotic AIS and might be potentially useful as a prognostic biomarker of the disease.

Topics: Adiponectin; Aged; Area Under Curve; Brain Ischemia; Cohort Studies; Disease Progression; Female; Humans; Leptin; Logistic Models; Male; Middle Aged; Multivariate Analysis; Prognosis; Prospective Studies; Recovery of Function; Resistin; Severity of Illness Index; Stroke; Tomography, X-Ray Computed

Depression is a frequent mood disorder that affects around a third of stroke patients and has been associated with poorer outcomes. Our aim was to determine whether there was a relationship between inflammatory markers (leptin) and post-stroke depression (PSD).. One hundred and ninety-one ischemic stroke patients admitted to the hospital within the first 24 hours after stroke onset were consecutively recruited and followed up for 3 months. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of leptin at admission. Based on the symptoms, diagnoses of depression were made in accordance with DSM-IV criteria for post-stroke depression at 3 month.. Forty-four patients (23.0%) were diagnosed as having major depression at 3 month. Patients with depression showed higher serum leptin levels at 3 month after stroke (32.2 [IQR, 20.8-57.7] v. 9.9 [IQR, 4.6-13.1]ng/ml, respectively; P = 0.000). Serum levels of leptin ≥20 ng/ml were independently associated with PSD [odds ratio (OR) 20.23, 95% confidence interval (CI) 9.11-51.26, P =  0.000], after adjusting for possible confounders.. Serum leptin levels elevated at admission were found to be associated with PSD and may provide a new proposal for the treatment of PSD.

Topics: Aged; Biomarkers; C-Reactive Protein; Cohort Studies; Depression; Female; Genetic Association Studies; Humans; Leptin; Male; Middle Aged; Risk Factors; Stroke

Leptin is a potent AMP kinase (AMPK) inhibitor that induces neuroprotection, neurogenesis, and angiogenesis when administered immediately after stroke. To dissociate these effects, we explored the effects of delayed administration of leptin, at 10 days after stroke onset, on neurogenesis and angiogenesis after stroke. Sabra mice underwent photothrombotic stroke and were treated with vehicle or leptin given either as a single dose or in triple dosing, 10 days later. Newborn cells were labeled with bromodeoxyuridine. Functional outcome was studied with the neurological severity score for 90 days poststroke, and the brains were then evaluated via immunohistochemistry. Final infarct volumes did not differ between the groups. Exogenous leptin led to significant increments in the number of proliferating BrdU(+) cells in the subventricular zone and in the cortex abutting the lesion (2.5-fold and 1.4-fold, respectively). There were significant increments in the number of newborn neurons and glia (4- and 3.4-fold, respectively) in leptin-treated animals. Leptin also significantly increased the number of blood vessels in the perilesioned cortex. However, animals treated with leptin failed to demonstrate significantly better functional states. In conclusion, leptin induces neurogenesis and angiogenesis even when given late after stroke but does not lead to better functional outcome in this delayed-treatment paradigm. These results suggest that the main beneficial effects of leptin after stroke are associated with its early neuroprotective role rather than with its proneurogenic or proangiogenic effects.

Topics: Animals; Blood Vessels; Brain Infarction; Bromodeoxyuridine; Cell Proliferation; Disease Models, Animal; Drug Administration Schedule; Glial Fibrillary Acidic Protein; Leptin; Male; Mice; Neovascularization, Physiologic; Neurogenesis; Neuroprotective Agents; Phosphopyruvate Hydratase; Platelet Endothelial Cell Adhesion Molecule-1; Stroke; Time Factors

The association between adiposity and adipocytes and risk of stroke in older adults is uncertain. We have examined the association between adiposity measures and adipocytes (adiponectin and leptin) with incident stroke events in older men.. Prospective study of 3411 men aged 60 to 79 years with no previous diagnosis of myocardial infarction, heart failure, or stroke followed-up for an average of 9 years, during which there were 192 incident major stroke events.. In age-adjusted analyses, body mass index and waist circumference were not significantly associated with risk of stroke in older men, although obese men (body mass index >30 kg/m(2)) showed the lowest risk of stroke. Despite the strong positive correlation between leptin and body mass index and waist circumference, risk of stroke was significantly increased in those in the top quartile of the leptin distribution. The increased risk remained after adjustment for potential confounders, including systolic blood pressure (adjusted hazard ratios top quartile versus bottom quartile: 2.03; confidence interval, 1.27-3.27]). Further adjustment for markers of inflammation (c-reactive protein), endothelial dysfunction (von Willebrand factor), fibrinolytic activity (d-dimer), and γ-glutamyl transferase attenuated the increased risk, but risk remained significantly increased (adjusted hazard ratios, 1.73; confidence interval, 1.06-2.83]). By contrast, no association was seen between adiponectin and risk of stroke.. Conventional adiposity measures were not associated with increased stroke risk in older men. However, leptin (a good marker of percent fat mass), but not adiponectin, predicted stroke, suggesting a link between fat mass and stroke risk.

Topics: Adipokines; Adiponectin; Adiposity; Age Factors; Aged; Biomarkers; Follow-Up Studies; Humans; Incidence; Leptin; Male; Middle Aged; Prospective Studies; Risk Factors; Sex Factors; Stroke

Experimental studies have indicated that adipocytokines are associated with vascular diseases with regard to the pathology of atherosclerotic plaque. We hypothesized that the strength of the associations between adipocytokines and stroke would differ between ischemic stroke subtypes.. A total of 96 acute ischemic stroke patients (within 5 days from onset) and 48 non-stroke subjects were analyzed in this study. Stroke patients were comprised of 26 strokes due to large artery atherosclerosis (LAA) and 72 non-LAA strokes. Venous blood from all participants was drawn after an overnight fast, and serum levels of leptin, adiponectin and resistin were measured by multiple sandwich immunoassay techniques.. Compared with non-LAA strokes, patients with LAA strokes had lower levels of serum adiponectin (6.4 ± 3.1 vs. 8.5 ± 3.9 μg/mL; P=0.04), and a higher level of leptin-to-adiponectin ratio (L:A ratio; 1.6 ± 1.4 vs. 0.9 ± 0.9; P<0.01). Multinomial logistic regression analyses showed that, although none of the adipocytokines was associated with non-LAA strokes, lower adiponectin (adjusted OR, 0.79 per 1-μg/mL increase; 95% CI, 0.64-0.98), higher leptin (aOR, 1.12 per 1-ng/mL increase; 95% CI, 1.004-1.25) and higher L:A ratio (aOR, 2.93 per 1-quartile increase; 95% CI, 1.39-6.15) showed significant associations with increased odds of having LAA stroke, compared to non-stroke subjects.. From our study, we documented that leptin and adiponectin had differential association patterns with ischemic stroke according to the stroke subtype. Careful consideration of the heterogeneity of stroke subtypes would be warranted in studying the utility of biomarkers including adipocytokines.

Topics: Adiponectin; Aged; Brain Ischemia; Female; Humans; Intracranial Arteriosclerosis; Leptin; Male; Middle Aged; Predictive Value of Tests; Stroke

Leptin is an adipokine that in vitro enhances agonist-induced platelet aggregation and adipokine expression. Hyperleptinaemia represents a risk factor for cardiovascular disease. We conducted a prospective evaluation of the potential link between blood platelet activation and plasma leptin levels in post-stroke patients. Using five-colour flow cytometry, the platelet surface expression of CD40L, CD62P, the subpopulations of monocyte-platelet aggregates and platelet-derived microparticles (PMPs) as well as the plasma leptin, soluble leptin receptor (sOb-R), leptin/sOb-R ratio, the plasma adiponectin, and leptin/adiponectin ratio were assessed in 98 stroke patients on the first (V₀), 10th (V₁ ) and 90th (V₂) day after stroke and once in 78 age-, gender- and vascular risk factor-matched disease controls. We demonstrated that at V0 leptin resistance, defined as leptin/sOb-R ratio, was higher than in the controls [1.1 (0.5-1.8 vs. 0.5 (0.2-1.1); p=0.02]. After adjustment according to the factors which influence platelet activation, we confirmed the relationship between percentage of circulating PMPs and plasma leptin level (B=0.18; p=0.02) or the leptin/sOb-R ratio (B=0.23; p=0.02) in normal-weight subjects in the acute phase of stroke. No correlation could be demonstrated between the adipokine parameters and the percentage of monocyte-platelet aggregates or expression of platelet pro-inflammatory glycoproteins. In conclusion, formation of PMPs on the first day following an ischaemic stroke shows a positive correlation with leptin levels and with resistance to leptin. Leptin level does not seem to affect the expression of platelet surface proinflammatory glycoproteins.

Topics: Acute Disease; Adiponectin; Aged; Blood Platelets; CD40 Ligand; Cell Separation; Cell-Derived Microparticles; Disease Progression; Female; Flow Cytometry; Humans; Leptin; Male; Middle Aged; Monocytes; P-Selectin; Platelet Activation; Prospective Studies; Stroke

Stroke, due to its worldwide prevalence, is not only a medical challenge, but also a serious social problem. Recently, ongoing research has examined whether there are associations between adipose tissue hormones and the risk, mechanisms and course of stroke. The aim of our study was to determine whether there are significant differences in blood concentrations of insulin, adiponectin, leptin, resistin and in insulin resistance among patients in the acute phase of ischaemic stroke, compared to healthy subjects. In addition, we wanted to investigate if those biochemical values show a correlation with the neurological condition of our patients.. Adiponectin, leptin, resistin and insulin were measured in patients (n = 69) with first-ever ischaemic stroke (confirmed by CT), using specific electrochemoluminescence, radioimmunoassay and ELISA methods. Neurological evaluation was performed using Barthel ADL index on the day of admission and on the ninth day of hospitalisation. Insulin resistance value was obtained via the HOMA-IR calculator. Data was compared to that of healthy individuals (n = 26).. Insulin concentration (51.08 v. 17.02 uU/mL) and HOMA-IR value (6.3 v. 2.2) were significantly higher in the study group. Leptin (14.98 v. 10.47 ng/mL) and resistin (28.92 v. 12.25 ng/mL) levels were elevated among the stroke survivors compared to controls, but no significant difference was noted in adiponectin. Negative correlations of adiponectin level and Barthel score were observed.. Hyperinsulinaemia and insulin resistance are involved in the pathogenesis of ischaemic stroke. Hyperleptinaemia and hyperresistinaemia play a role in the mechanism of stroke. The severity of stroke is associated with adiponectin blood concentration.

Topics: Adiponectin; Adult; Aged; Aged, 80 and over; Biomarkers; Female; Homeostasis; Humans; Insulin; Leptin; Male; Middle Aged; Poland; Resistin; Stroke

Leptin is an adipokine with both protective and harmful effects on the cardiovascular (CV) system. Prior studies evaluating the association between leptin and CV outcomes have yielded conflicting results. Thus, we sought to investigate the relationship between leptin and CV events and mortality in patients with chronic stable coronary artery disease (CAD).. We performed a prospective cohort study of 981 outpatients with stable CAD. Leptin levels were measured in fasting venous samples at baseline. We used proportional hazards models to evaluate the association of baseline leptin with subsequent CV events (myocardial infarction, stroke, transient ischemic attack) and death.. During a mean follow-up of 6.2±2.1 years, there were 304 deaths, 112 myocardial infarctions, and 52 strokes/TIAs. In models adjusted for age, sex, and race, low leptin was associated with a 30% increased risk of the combined outcome (HR 1.30, CI 1.05-1.59, p=0.01). After further adjustment for obesity, traditional CV risk factors and biomarkers, low leptin remained associated with a 37% increased risk of events (HR 1.37, CI 1.06-1.76, p=0.02).. Low leptin is associated with increased CV events and mortality in patients with stable coronary artery disease. This association is independent of known factors affecting leptin levels, including gender and obesity.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Chi-Square Distribution; Chronic Disease; Coronary Artery Disease; Down-Regulation; Female; Humans; Ischemic Attack, Transient; Kaplan-Meier Estimate; Leptin; Male; Middle Aged; Myocardial Infarction; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; San Francisco; Stroke

Adipose tissue is considered an endocrine organ that secretes adipokines, which possibly mediate the effects of obesity on the risk of cardiovascular disease. However, there are yet limited prospective data on the association between circulating adipokine levels and the risk of ischemic stroke. We aimed to examine the associations of 3 adipokines (adiponectin, leptin, and resistin) with the risk of ischemic stroke.. We conducted a prospective nested case-control study (972 stroke cases and 972 matched control subjects) within the Women's Health Initiative Observational Study cohort. The control subjects were matched to cases on age, race/ethnicity, date of study enrollment, and follow-up time.. Adipokine levels were associated with established stroke risk factors such as obesity and systolic blood pressure. Adjusted for body mass index, the ORs for incident ischemic stroke comparing the highest (Quartile 4) with the lowest quartile (Quartile 1) were 0.81 (95% CI, 0.61 to 1.08; P trend=0.068) for adiponectin, 1.15 (95% CI, 0.83 to 1.59; P trend=0.523) for leptin, and 1.57 (95% CI, 1.18 to 2.08; P trend=0.002) for resistin. The association for resistin remained significant even after accounting for established stroke risk factors (OR, 1.39; 95% CI, 1.01 to 1.90; P trend=0.036). Further adjustment for markers for inflammation, angiogenesis, and endothelial function also did not affect our results.. Circulating levels of resistin, but not those of adiponectin or leptin, are associated with an increased risk of incident ischemic stroke in postmenopausal women, independent of obesity and other cardiovascular disease risk factors.

Topics: Adiponectin; Aged; Blood Pressure; Case-Control Studies; Female; Humans; Ischemia; Leptin; Middle Aged; Postmenopause; Prospective Studies; Resistin; Risk; Risk Factors; Stroke

Leptin is a potent AMP kinase (AMPK) inhibitor that is central to cell survival. Hence, we explored the effects of leptin on neurogenesis and angiogenesis after stroke. Neural stem cells (NSC) were grown as neurospheres in culture and treated with vehicle or leptin and neurosphere size and terminal differentiation were then determined. We then explored the effects of leptin on endogenous repair mechanisms in vivo. Sabra mice underwent photothrombotic stroke, were given vehicle or leptin and newborn cells were labeled with Bromo-deoxy-Uridine. Functional outcome was studied with the neurological severity score for 90 days post stroke and the brains were then evaluated with immunohistochemistry. In a subset of animals the brains were also evaluated for changes in the expression of leptin receptor and AMPK. In vitro, leptin led to a 2-fold increase in neurosphere size but did not change the differentiation of newborn cells. Following stroke, exogenous leptin led to a 4-fold increase in the number of NSC in the cortex abutting the lesion. There was a 1.5-fold increase in the number of newborn neurons and glia in leptin treated animals. Leptin also significantly increased the number of blood vessels in the peri-lesioned cortex. Leptin treated mice had increased expression of leptin receptor and increased phosphorylated AMPK concentration. Animals treated with leptin also had significantly better functional states. In conclusion, leptin induces neurogenesis and angiogenesis after stroke and leads to increased leptin receptor and pAMPK concentrations. This may explain at least in part the better functional outcome observed in leptin treated animals after stroke.

Topics: AMP-Activated Protein Kinase Kinases; Animals; Blood Vessels; Brain Infarction; Bromodeoxyuridine; CD3 Complex; Cell Count; Cell Differentiation; Cells, Cultured; Disability Evaluation; Disease Models, Animal; Dose-Response Relationship, Drug; Embryo, Mammalian; Fibroblast Growth Factors; Glial Fibrillary Acidic Protein; Leptin; Mice; Neovascularization, Pathologic; Neural Stem Cells; Neurogenesis; Neuroprotective Agents; Protein Kinases; Receptors, Leptin; Stroke; Time Factors; TRPV Cation Channels; Tubulin

Fat tissue is an important endocrine organ that produces a number of hormones and cytokines (leptin, adiponectin, resistin, plasminogen activator inhibitor-1, Tumour necrosis factor TNF α) with essential roles in regulation of many physiological functions.. We targeted implications of adipokines in ischemic stroke patients. Patients with acute stroke were examined (n=145) and the results were compared with the control group (n=68). We have examined potential associations between leptin, adiponectin and ghrelin, and different types of stroke and traditional risk factors.. Significantly higher levels of leptin and lower levels of adiponectin and ghrelin were confirmed in the stroke group. The level of leptin in women with stroke was three-times higher than in men, and the leptin levels positively correlated with obesity in both sexes. Ghrelin levels correlated mildly with triglyceride levels, and were dominant in men with cardioembolic stroke. Adiponectin levels were not different between men and women with acute stroke, and correlated with atherothrombotic and lacunar stroke types in men.. Adipokines and ghrelin play an important role in ischemic stroke, but their function in stroke subtypes seems to be different and sex influenced. More research is required to confirm our results.

Topics: Adiponectin; Aged; Brain Ischemia; Female; Ghrelin; Humans; Intracranial Arteriosclerosis; Intracranial Embolism; Leptin; Male; Middle Aged; Risk Factors; Sex Distribution; Stroke; Stroke, Lacunar; Triglycerides

To examine the association of increased plasma leptin concentration with prevalent stroke and coronary heart disease (CHD) and to examine the genetic contributions of leptin to this association in the Jackson Heart Study cohort.. A cohort of 5170 participants aged 21-84 years who underwent Exam I during 2000-2004 was analysed. Odds ratios (OR) of prevalent stroke and CHD were calculated using a logistic regression model adjusted for age, smoking, hypertension and waist circumference (WC). Variance component analysis was used to partition the phenotypic variance of leptin into the polygenic and environmental components.. The prevalence of stroke and CHD was 4.04% and 5.85% in women, and 4.88% and 8.92% in men, respectively. Body mass index (BMI) and WC were highly correlated with leptin both in men and women. In multivariate analysis stratified by sex, leptin was significantly associated with stroke (OR = 1.97, 95% CI = 1.21-3.21) in women after adjustment for age, smoking, systolic blood pressure, BMI and WC (P = 0.0079). No significant association was observed in men. Heritability of sex-, age-adjusted log-transformed leptin for this cohort was 38.0% and 37.8% after further adjustment for WC and hypertension, respectively. In addition, a sibship effect was also found to be significant and explained 12.2% of the total variance of leptin (P = 0.007).. There is a significant association of leptin with stroke in women, which is partly influenced by the genetic factor. The findings suggest that leptinemia is an independent risk factor for stroke in African American women.

Topics: Adult; Aged; Aged, 80 and over; Cohort Studies; Coronary Disease; Cross-Sectional Studies; Female; Humans; Leptin; Male; Middle Aged; Mississippi; Prevalence; Risk Factors; Stroke; Up-Regulation; Young Adult

To investigate adipocytokines in patients with ischemic cerebrovascular disease and to develop an association between them.. In this study plasma adiponectin, leptin and Interleukin 6 (IL 6) concentration were measured by ELISA. Blood glucose and lipid profile was done by standard kit methods.. A total of 80 subjects with and without CVD were studied. The mean plasma level of IL6 of the forty patients with ischemic CVD was significantly higher than that of the forty subjects without CVD (41.64 + 2.50 versus 22.76 + 0.76 pg/mL; P < 0.001). The mean plasma level of adiponectin was significantly lower in patients with ischemic CVD than that of subjects without CVD (4.36 +/- 0.21 microg/mL versus 6.9 +/-0.241microg/mL; P < 0.001). Serum leptin concentrations were significantly higher (p < 0.001) in stroke patients (51.61 + 1.39) as compared with controls (37.76 + 1.207). Leptin levels were significantly negatively correlated with adiponectin (P < 0.01) and significantly positively correlated (P < 0.01) with interleukin 6 in stroke patients.. Present report provides additional support to the evidence of involvement of cytokines in inflammatory immune response of patients with cerebrovascular disease.

Topics: Adiponectin; Aged; Brain Ischemia; Cerebrovascular Disorders; Female; Humans; Inflammation; Interleukin-6; Leptin; Male; Middle Aged; Stroke

To clarify the association of circulating levels of leptin with risk for cardiovascular disease (CVD) events and new-onset diabetes in men and women.. We related baseline leptin levels to CVD events (n = 864) and incident diabetes (n = 289) in an elderly population (n = 5,672) over 3.2 years of follow-up.. In treatment-, age-, and country-adjusted models, leptin was not associated with risk of CVD in men (hazard ratio 1.02 [95% CI 0.90-1.16] per unit log-leptin increase) or women (1.05 [0.91-1.20]) but was associated with risk of diabetes in men (2.75 [2.14-3.52]) and women (1.54 [1.22-1.94]). After adjusting for classic risk factors and BMI, C-reactive protein, and glucose, the diabetes association retained significance in men (1.85 [1.30-2.63]) but not in women (0.89 [0.64-1.26]).. Leptin, similar to other markers of adiposity in general, is more strongly related to risk of diabetes than CVD in the elderly.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiovascular Diseases; Diabetes Mellitus; Female; Humans; Ireland; Leptin; Male; Myocardial Infarction; Netherlands; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Scotland; Stroke

Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a chemokine involved into the pathogenesis of atherosclerosis and has prognostic value in the acute and chronic phases in patients with acute coronary syndromes.. MCP-1/CCL2 concentration was measured in plasma fractions of 363 middle-aged overweight/obese individuals (aged 61 +/- 12 years, BMI 30.1 +/- 6.6 kg/m(2), 15% with type 2 diabetes, and 12% with impaired glucose tolerance) of a population survey carried out in 1990-1991 in Lombardy, Italy (Cremona Study), and cardiovascular disease (CVD) mortality was assessed in 2006 through Regional Health Registry files.. At baseline MCP-1/CCL2 was increased in individuals with type 2 diabetes (P < 0.05) and showed significant correlations with biochemical risk markers of atherosclerosis. After 15 years, among the 363 subjects, there were 82 deaths due to CVD. In univariate analysis age, sex, fasting glucose and insulin, fibrinogen, glucose tolerance status, smoking habit, and MCP-1/CCL2 were associated with CVD mortality. Age, sex, fasting serum glucose, MCP-1/CCL2, and smoking habit maintained an independent association with CVD mortality in multiple regression analysis. In a subgroup of 113 subjects in whom data for C-reactive protein (CRP) were available, its level was not predictive of CVD mortality.. In middle-aged overweight/obese individuals MCP-1/CCL2 was independently associated with CVD mortality. Further studies will be necessary to establish its role as a surrogate biomarker and as a potential therapeutic target.

Topics: Atherosclerosis; Biomarkers; Body Mass Index; C-Reactive Protein; Cardiovascular Diseases; Chemokine CCL2; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Glucose Tolerance Test; Humans; Insulin; Italy; Leptin; Life Style; Middle Aged; Prognosis; Risk Factors; Stroke

Although epidemiological studies reveal an increased incidence of obesity and an association between obesity and the prevalence/severity of ischemic stroke, little is known about the mechanisms that link obesity to ischemic stroke. This study tested the hypothesis that obesity exacerbates the cerebrovascular dysfunction and tissue injury induced by brain ischemia and reperfusion.. The adhesion of leukocytes and platelets in cerebral venules, blood-brain barrier permeability, brain water content, and infarct volume were measured in wild-type, obese (ob/ob), and leptin-reconstituted ob/ob mice subjected to 30 minutes middle cerebral artery occlusion and reperfusion. Tissue and plasma cytokine levels were determined by cytometric bead array, and a role for monocyte chemoattractant protein-1 and interleukin-6 was assessed using blocking antibodies.. Compared with wild-type mice, ob/ob exhibited larger increases in leukocyte and platelet adhesion, blood-brain barrier permeability, water content, and infarct volume after middle cerebral artery occlusion-reperfusion. Reconstitution of leptin in ob/ob mice tended to further enhance all reperfusion-induced responses. Ob/ob mice also exhibited higher plasma levels of monocyte chemoattractant protein-1 and interleukin-6 than wild-type mice. Immunoneutralization of monocyte chemoattractant protein-1, but not interleukin-6, reduced infarct volume in ob/ob mice.. Obesity worsens the inflammatory and injury responses to middle cerebral artery occlusion and reperfusion by a mechanism independent of leptin deficiency. monocyte chemoattractant protein-1 appears to contribute to the exaggerated responses to ischemic stroke in obese mice.

Topics: Animals; Blood-Brain Barrier; Brain Ischemia; Capillary Permeability; Cell Adhesion; Cerebral Infarction; Cerebrovascular Circulation; Chemokine CCL2; Encephalitis; Infarction, Middle Cerebral Artery; Interleukin-6; Leptin; Leukocytes; Male; Mice; Mice, Obese; Obesity; Platelet Adhesiveness; Reperfusion Injury; Stroke

Leptin, an adipose tissue-derived hormone, has been linked to cardiovascular outcomes; however, data are limited in the United States population, especially women. To assess the association between leptin concentrations and history of myocardial infarction (MI) and stroke independently of traditional cardiovascular risk factors, we analyzed data from 6,239 subjects (mean age 47 years; 3,336 women) with measurements of serum leptin and full assessment of cardiovascular risk factors from the National Health and Nutrition Examination Survey (NHANES) III. Logistic regression was used to estimate the cross-sectional association of leptin concentrations (highest quartile versus lowest quartile) and history of MI, stroke, and the composite end point of MI or stroke (MI/stroke). Gender-specific models of leptin were adjusted for age, race, dyslipidemia, hypertension, diabetes, smoking, and obesity status. There were 212 men with MI/stroke (5.4%), 154 with MI (4.1%), and 82 with stroke (1.7%). There were 135 women with MI/stroke (2.6%), 74 with MI (1.5%), and 78 with stroke (1.4%). In multivariate analysis, high leptin level was significantly and independently associated with MI/stroke in men (odds ratio [OR] 2.41, 95% confidence interval [CI] 1.20 to 4.93) and women (OR 4.26, 95% CI 1.75 to 10.73); with MI in men (OR 3.16, 95% CI 1.40 to 7.37) and women (OR 3.96, 95% CI 1.29 to 12.72), and with stroke in women (OR 3.20, 95% CI 1.04 to 10.54) but not in men (OR 1.37, 95% CI 0.38 to 3.88). In conclusion, in the United States population, increased leptin concentrations are significantly associated with MI/stroke in men and women independently of traditional cardiovascular risk factors and obesity status.

Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Leptin; Male; Middle Aged; Models, Theoretical; Multivariate Analysis; Myocardial Infarction; Risk Factors; Stroke; United States

Prolactin and leptin are newly recognised platelet co-stimulators due to potentiation of ADP-induced platelet aggregation. Elevated leptin levels have recently been found to be a risk factor for ischemic stroke in both men and women, and especially in combination with increased blood pressure for hemorrhagic stroke in men. Until now an association between hyperprolactinemia and ischemic stroke has not been investigated systematically. We determined plasma prolactin and leptin levels as well as platelet P-selectin expression in 36 patients with ischemic stroke or transient ischemic attack and detected a significant correlation between increased prolactin values and enhanced ADP stimulated P-selectin expression on platelets. In contrast, no correlation of leptin values with platelet P-selectin expression was found. Next we determined plasma prolactin and leptin as well as acquired and congenital risk factors of thrombophilia in patients with first-ever non-hemorrhagic stroke with or without atrial fibrillation. Excluding patients with such preexisting risk factors, 21 patients with and 59 patients without atrial fibrillation were identified. Patients without atrial fibrillation revealed significantly higher plasma prolactin levels than patients with atrial fibrillation. Furthermore, the influence of aspirin or clopidogrel on prolactin stimulated P-selectin expression in vitro was tested, showing that aspirin was without effect, whereas clopidogrel significantly inhibited platelet P-selectin expression. In conclusion, hyperprolactinemia might be a novel risk factor for stroke mediating its thrombogenic effect through enhanced platelet reactivity, and this might correspond to a higher efficacy of antiplatelet combination therapy with clopidogrel compared to aspirin therapy alone.

Topics: Aged; Aged, 80 and over; Aspirin; Brain Ischemia; Clopidogrel; Female; Humans; Ischemic Attack, Transient; Leptin; Male; Middle Aged; P-Selectin; Platelet Activation; Prolactin; Retrospective Studies; Risk Factors; Stroke; Thrombophilia; Ticlopidine

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

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

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

To assess the relationships between circulating levels of proinflammatory cytokines and adrenocortical hormones and leptin early after stroke.. Blood samples were collected four times daily the first two days after stroke, twice daily the next 4 days and four times at day 7. Cognitive function and functional outcome was measured at admittance and at day 7.. Consecutive inclusion of patients admitted to the stroke unit at Umeâ University Hospital.. Eight men and 4 women with acute stroke and 10 healthy volunteers.. Levels and diurnal variations of plasma proinflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), serum adrenocortical hormones (cortisol and DHEA) and leptin, and MMSE, SSS, and ADL scores.. A significant correlation was present between IL-6 and cortisol levels the first two days after stroke (P < 0.05). In patients with a disturbed diurnal rhythm of cortisol, cortisol and leptin levels were increased (68% and 81% increase, respectively), whilst DHEA levels were unaltered. Half of the patients displayed an abnormal diurnal rhythmicity of leptin at the end of the week. Median TNF-alpha levels for the first two days after stroke also correlated to median leptin levels at the end of the week (P < 0.05). Median IL-6 levels correlated to severity of paresis on days 1 and 7 and to MMSE scores on day 7 (P < 0.05).. Neuroendocrine disturbances are common and often profound early after stroke. Cytokines seem to be important modulators of these disturbances, including diurnal rhythmicity of cortisol and leptin.

Topics: Adrenocorticotropic Hormone; Aged; Aged, 80 and over; Body Mass Index; Case-Control Studies; Circadian Rhythm; Cognition Disorders; Dehydroepiandrosterone; Female; Humans; Hydrocortisone; Interleukin-6; Leptin; Linear Models; Male; Middle Aged; Multivariate Analysis; Paresis; Stroke; Tumor Necrosis Factor-alpha