Influence of Leptin on Arterial Distensibility

Abstract

Background-The mechanisms by which obesity increases the risk of atherosclerotic cardiovascular disease (CVD) are poorly understood. In experimental models, leptin, a hormone produced by adipose tissue, has been shown adversely to affect vascular health. Therefore, we tested the hypothesis that high leptin concentrations are associated with lower arterial distensibility, an index of circulatory function relevant to the atherosclerotic process. Methods and Results-Noninvasive, high-resolution, vascular ultrasound was used to measure brachial artery distensibility in 294 healthy adolescents (aged 13 to 16 years) who had a broad range of body mass indexes. Fat mass was measured by bioelectric impedance analysis; fasting serum leptin concentration by radioimmunoassay; and lipid profile, fasting insulin, glucose, and C-reactive protein concentrations by standard laboratory techniques. Higher leptin concentrations were associated with impaired arterial distensibility (regression coefficient, Ϫ1.3% change in arterial distension per 10% increase in leptin; 95% CI, Ϫ1.9% to Ϫ0.8%; PϽ0.001). This association was independent of fat mass, blood pressure, and C-reactive protein, fasting insulin, or LDL cholesterol concentrations. Conclusions-Elevation in leptin was associated with impaired vascular function, independent of the metabolic and inflammatory disturbances associated with obesity. Our observations are consistent with data from experimental models and suggest that high leptin concentration is an important mechanism for the adverse influence of body fatness on CVD.

Association between non-alcoholic fatty liver disease and arterial stiffness in the non-obese, non-hypertensive, and non-diabetic young and middle-aged Chinese population

“…Several mechanisms have been suggested, such as an increase in whole-body insulin resistance and abnormal secretion of adipose cytokines, including decreased adiponectin and increased leptin levels (Singhal et al, 2002;Angulo et al, 2004;Machado and Cortez-Pinto, 2005;Mahmud and Feely, 2005;Targher et al, 2006b;Targher and Arcaro, 2007). Overall, insulin resistance and adipose cytokines could explain the association between NAFLD and arterial stiffness.…”

Endothelial dysfunction and arterial abnormalities in childhood obesity

“…47 Furthermore, gender-specific analyses from this study demonstrate that in adolescent males, markers of anthropometry (BMI, fat mass and skinfolds -but not waist-hip-ratio) and serum insulin are related to brachial artery distensibility. These correlations were not apparent in adolescent females, with only leptin being correlated with arterial distensibility (P ¼ 0.08).…”

“…86,87 Additionally, these cardiovascular risk factors are all associated with vascular endothelial dysfunction. 88 Indeed, studies in children and adults examining the association between obesity and endothelial dysfunction have identified insulin resistance, 34,35,89 glucose intolerance, 48,57 serum lipoprotein and apolipoprotein levels, 34,49 adipocytokines, 47 inflammation, 40,41 oxidative stress 90 and endothelial nitric oxide synthase 91 as possible pathophysiological intermediaries. Much recent research has focused on the role of adipocytokines and other obesity-related peptides as important molecules in the pathophysiological link between increased adiposity and cardiovascular disease.…”

Effects of Angiotensin‐Converting Enzyme Inhibition on Leptin and Adiponectin Levels in Essential Hypertension

“…The cardiovascular protective effects of adiponectin are mediated by anti-inflammatory, insulin-sensitizing and antiatherogenic mechanisms [4][5][6]. On the other hand, hyperleptinaemia promotes cardiovascular remodelling [7,8] mainly by increasing sympathetic nervous system activity [9]. Indeed, increased leptin levels may predict development of hypertension, independent of BMI and insulin resistance [10].…”