leptin and Cardiomyopathy--Hypertrophic

A case of Berardinelli-Seip syndrome, a congenital generalised lipodystrophy, is reported. Symptoms first appeared when the patient was 20 years old. She showed severe insulin resistance as well as micro- and macro-angiopathic complications, including chronic kidney disease, which required renal replacement therapy with peritoneal dialysis. The patient's clinical course was reviewed since paediatric age (when initial signs of the disease being already evident) to present time. Berardinelli-Seip syndrome is very uncommon, and the present case is particularly rare because it is the only case (at least as reported in the literature) in a patient receiving dialysis.

Topics: Acromegaly; Cardiomyopathy, Hypertrophic; Child; Delayed Diagnosis; Diabetic Nephropathies; Diagnosis, Differential; Exons; Female; Glomerulonephritis, Membranoproliferative; GTP-Binding Protein gamma Subunits; Humans; Insulin Resistance; Leptin; Lipodystrophy, Congenital Generalized; Peritoneal Dialysis, Continuous Ambulatory

The identification of the adipocyte as a source of production of biologically-active peptides has materialized into an active area of research related to the role of these peptides in physiology and pathophysiology. Moreover, this research has resulted in the identification of the adipocyte as an endocrine organ producing potent bioactive compounds. An increasing number of these adipokines are being identified, the first of which was leptin, a product of the obesity gene whose primary function is to act as a satiety factor but which is now known to exert a myriad of effects. It is now recognized that virtually all adipokines produce effects on numerous organ systems including the heart and many of these, including leptin, are produced by cardiac tissue. Here we focus primarily on the diverse effects of leptin on the heart especially as it pertains to hypertrophy and discuss the potential cell signaling mechanisms underlying their actions. Current evidence suggests that leptin is a cardiac hypertrophic factor and from clinical studies there is evidence that hyperleptinemia is associated with cardiovascular risk especially as it pertains to heart failure. While more substantial research needs to be carried out, leptin may represent a potential link between obesity, which is associated with hyperleptinemia, and increased cardiovascular risk.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cardiovascular System; Disease Progression; Heart Failure; Humans; Leptin; Models, Cardiovascular; Receptors, Leptin; Signal Transduction

The satiety factor leptin has received extensive attention especially in terms of its potential role in appetite suppression and regulation of energy expenditure. Once considered to be solely derived from adipose tissue, which accounts for the greatly increased levels observed in obese subjects, it is now apparent that leptin can be produced by a multiplicity of tissues, including the heart, where it appears to function in an autocrine and paracrine manner. Plasma leptin concentrations are also elevated in patients with heart disease including those with congestive heart failure. Leptin exerts its biological effects via a family of receptors termed Ob-R. In cardiac cells, one of leptin's primary actions is to produce cardiomyocyte hypertrophy through multifaceted cell signaling mechanisms including stimulation of mitogen-activated protein kinase and activation of the RhoA/Rho kinase (ROCK) pathway. The hypertrophic effect of leptin suggests that it may contribute to myocardial remodeling after cardiac injury and offers the potential targeting of the leptin system as a novel cardiac therapy.

Topics: Adipose Tissue; Cardiomyopathy, Hypertrophic; Humans; Leptin; Mitogen-Activated Protein Kinases; Myocardium; Myocytes, Cardiac; Obesity; Risk Factors; Signal Transduction

Leptin is an adipokine, which is in humans with cardiac disease suspected to be involved in myocardial remodeling and thrombus formation. In cats, however, it is not known whether leptin plays a role in cardiac disease, i.e. hypertrophic cardiomyopathy (HCM) and the presence of an atrial thrombus (AT). The objective of the study was therefore to establish whether leptin is transcribed in the feline myocardium and to compare myocardial leptin mRNA concentrations in cats with HCM with and without AT, and in cats without cardiac diseases. Myocardial samples from 15 cats with HCM (five of these with AT), and 12 cats without cardiac diseases were investigated for leptin mRNA expression using quantitative reverse transcriptase PCR, and the transcription levels were correlated with those obtained for a range of cytokines and remodeling parameters. Leptin mRNA expression was detected in the myocardium in all heart regions, with generally higher concentrations in the atria than in the ventricles. Cats with HCM exhibited higher atria and ventricular leptin transcription than cats without cardiac diseases, but reduced ventricular transcription levels in the presence of AT. A positive correlation between leptin, cytokine and remodeling marker transcription levels was observed. The present study shows that leptin is constitutively transcribed in the feline myocardium. The observed increase in leptin mRNA concentrations in the myocardium from cats with HCM and the reduction when an AT is present suggests varying gene activation in different stages of the disease and a potential involvement of leptin in the feline cardiac remodeling process.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Cytokines; Gene Expression Regulation; Heart Atria; Leptin; Male; Myocardium; RNA, Messenger; Thrombosis

Studies conducted so far have shown that patients with left ventricular hypertrophy have increased adiponectin levels; however, these studies were performed only in resting condition.. The aim of the study was to compare adiponectin, resistin, and leptin levels (at rest and after exercise) between patients with hypertrophic cardiomyopathy (HCM) and healthy controls. Additionally, we examined potential relationships between the levels of the 3 adipokines and the left ventricular outflow tract (LVOT) gradient both at rest and at peak exercise.. We studied 29 patients with HCM (mean age 42.7 ±11.9 years, 16 men and 13 women). The control group included 19 healthy subjects matched for age-, sex-, and the body mass index. After echocardiographic examination in a supine position, all patients were placed in an upright position and treadmill exercise test was performed with simultaneous continuous echocardiographic monitoring of the LVOT gradient. Adiponectin, resistin, and leptin levels were measured immediately prior to exercise in a supine position and at peak exercise in an upright position.. At baseline (at rest), adiponectin levels tended to be increased in patients with HCM (P = 0.09), while resistin and leptin levels were significantly higher in patients with HCM than in healthy controls. In HCM patients, exercise induced an increase in adiponectin (20.74 ±7.95 vs. 22.52 ±8.10 μg/ml, P <0.05), a decrease in leptin (22.78 ±6.08 vs. 20.63 ±5.57 ng/ml, P <0.05), and no significant effect on resistin. In the control group, all biomarkers mildly decreased at peak exercise (adiponectin 19.23 ±5.43 vs. 18.66 ±5.31 μg/ml P = 0.044), resistin 14.80 ±1.87 vs. 13.87 ±1.21 ng/ml, P = 0.030), (leptin 14.34 ±4.74 vs. 13.50 ±3.98 ng/ml, P = 0.045). In HCM patients, neither resting nor peak exercise values of the LVOT gradient correlated with any levels of adipokines.. In patients with HCM, but not in healthy individuals, moderate exercise induced an increase in adiponectin levels and a decrease in leptin levels independent of a rise in the LVOT gradient. The potential cardioprotective role of adiponectin during exercise stress in HCM requires further studies.

Topics: Adipokines; Adiponectin; Adult; Cardiomyopathy, Hypertrophic; Case-Control Studies; Exercise; Female; Humans; Leptin; Male; Middle Aged; Resistin