leptin and Cardiomyopathy--Dilated

The recent studies demonstrated that obese heart failure patients have better prognosis - "obesity paradox". The aim of the study was to evaluate the relationship between body mass index (BMI), leptin and adiponectin concentrations and prognosis in patients with heart failure due to non ischeamic dilated cardiomyopathy (NIDCM).. 128 patients with NIDCM were included and followed-up for three years. Leptin and adiponectin were measured at baseline using commercially available ELISA tests. Clinical data, routine laboratory parameters, NT-proBNP were assessed as risk factors for reaching the study endpoints: urgent heart transplantation (B), death (C), or combined endpoint death or urgent heart transplantation (D).. Patient with adverse outcome had lower BMI and higher NT-proBNP concentration. Leptin was significantly elevated in group C and adiponectin was higher in groups B and D than in survived patients. Patients with leptin concentration below median or with adiponectin concentration above median were more often transplanted in three years follow-up (p = 0.029, p = 0.022, respectively). The cumulative probability of death was greater in patients with concentration of leptin above median (p = 0.024). In the multivariable Cox proportional hazards analyses, increasing leptin and lower BMI were predictors of death. Adiponectin was associated with higher risk of heart transplantation. Both an inverse association of BMI and positive association of leptin and adiponectin with combined endpoint were discovered. Further adjustment to established risk factors abolished association between combined endpoint and BMI, and modestly attenuate with adiponectin and leptin concentration.. Evaluation of adiponectin and leptin concentrations was more useful than BMI in prediction of unfavourable outcome in patients with NIDCM. (Endokrynol Pol 2017; 68 (1): 26-34).

Topics: Adiponectin; Adult; Body Mass Index; Cardiomyopathy, Dilated; Female; Humans; Leptin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Dilated cardiomyopathy (DCM) is a common cause of heart failure, and identification of early pathogenic events occurring prior to the onset of cardiac dysfunction is of mechanistic, diagnostic, and therapeutic importance. The work characterized early biochemical pathogenesis in TO2 strain hamsters lacking delta-sarcoglycan. Although the TO2 hamster heart exhibits normal function at 1 month of age (presymptomatic stage), elevated levels of myeloperoxidase, monocyte chemotactic protein-1, malondialdehyde, osteopontin, and alkaline phosphatase were evident, indicating the presence of inflammation, oxidative stress, and osteogenic phenotype. These changes were localized primarily to the myocardium. Derangement in energy metabolism was identified at the symptomatic stage (4 month), and is marked by attenuated activity and expression of pyruvate dehydrogenase E1 subunit, which catalyzes the rate-limiting step in aerobic glucose metabolism. Thus, this study illustrates differential involvement of oxidative stress, osteogenic phenotype, and glucose metabolism in the initiation and early progression of delta-sarcoglycan-null DCM.

Topics: Animals; Biomarkers; Cardiomyopathy, Dilated; Cricetinae; Cricetulus; Energy Metabolism; Glucose; Insulin; Leptin; Male; Myocardium; Osteogenesis; Oxidative Stress; Phenotype; Protein Subunits; Pyruvate Dehydrogenase Complex; Sarcoglycans; Tissue Extracts

Alpha-lipoic acid (alpha-LA) mimics the hypothalamic actions of leptin on food intake, energy expenditure, and activation of AMP-activated protein kinase (AMPK). To determine if, like leptin, alpha-LA protects against cardiac lipotoxicity, alpha-LA was fed to transgenic mice with cardiomyocyte-specific overexpression of the acyl CoA synthase (ACS) gene. Untreated ACS-transgenic mice died prematurely with increased triacylglycerol content and dilated cardiomyopathy, impaired systolic function and myofiber disorganization, apoptosis, and interstitial fibrosis on microscopy. In alpha-LA-treated ACS-transgenic mice heart size, echocardiogram and TG content were normal. Plasma TG fell 50%, hepatic-activated phospho-AMPK rose 6-fold, sterol regulatory element-binding protein-1c declined 50%, and peroxisome proliferator-activated receptor-gamma cofactor-1alpha mRNA rose 4-fold. Since food restriction did not prevent lipotoxicity, we conclude that alpha-LA treatment, like hyperleptinemia, protects the heart of ACS-transgenic mice from lipotoxicity.

Topics: Animals; Caloric Restriction; Cardiomyopathy, Dilated; Coenzyme A Ligases; Heart; Leptin; Mice; Mice, Transgenic; Myocardium; Thioctic Acid; Transcriptional Activation; Triglycerides

Leptin, a product of the ob gene, is known to increase energy expenditure. Given that chronic heart failure is a hypercatabolic state, we sought to determine whether congestive heart failure involves elevations in plasma leptin levels. Since leptin secretion is up-regulated by insulin, we also explored whether in congestive heart failure, a hyperinsulinaemic state, plasma leptin levels relate to plasma insulin levels.. Male patients with weight-stable congestive heart failure (n = 25, aged 55.5 +/- 2.0, mean +/- SEM, body mass index = 27.4 +/- 0.8, radionuclide left ventricular ejection fraction = 29.3 +/- 3.0%) and 18 controls, matched for age, sex and body fat (dual energy X-ray absorptiometry), underwent measurement of fasting plasma leptin (radioimmunoassay) and insulin levels.. Compared to controls, patients with congestive heart failure had higher plasma leptin [8.12 (-1.12, +1.31) vs 4.48 (-0.61, +0.70) ng.ml-1, mean +/- asymmetrical SEM, P = 0.003], 41.5% higher plasma leptin per percent body fat mass (P < 0.001), and higher fasting insulin levels [67.8 (-11.1, +13.3) vs 32.9 (-5.7, +6.9) pmol.l-1, P = 0.010]. In the congestive heart failure group, plasma leptin correlated with total body fat (r = 0.66) and fasting insulin (r = 0.68) (both P < 0.001). In multivariate regression analyses of the congestive heart failure group, fasting insulin (standardized coefficient = 0.41, P = 0.011) emerged as a predictor of plasma leptin levels, independent of total body fat (standardized coefficient = 0.73, P = 0.002, R2 = 0.66, P < 0.001).. Plasma leptin levels are raised in patients with congestive heart failure. The observation of a positive relationship between plasma leptin and insulin concentrations suggests that the insulin-leptin axis may be related to the increased energy expenditure observed in patients with congestive heart failure.

Topics: Adipose Tissue; Biomarkers; Body Mass Index; Cardiomyopathy, Dilated; Chronic Disease; Coronary Disease; Heart Failure; Humans; Hyperinsulinism; Insulin; Leptin; Male; Middle Aged; Proteins; Radioimmunoassay