Does Leptin Cause Vascular Disease?

n the past two decades, there has been a 2-to 4-fold increase in childhood obesity in the United States. The current epidemic of childhood obesity in the United States can be expected to cause a surge in cardiovascular disease in this generation. 1, 2Already, obesity-related illnesses account for nearly 300 000 deaths and about 100 billion in economic costs per year in the United States. Therefore, understanding the mechanisms by which obesity accelerates vascular disease has become ever more important. See p 1919 Mechanisms of Obesity-Induced Cardiovascular DiseaseObesity is associated with hypercholesterolemia, which is in some cases due to elevated levels of low-density lipoprotein cholesterol. Obesity-associated dyslipidemia is often due to metabolic syndrome, which is characterized by hypertriglyceridemia, hyperinsulinemia, hypertension, and reduced high-density lipoprotein cholesterol. 3Each component of the metabolic syndrome may contribute to the increased risk of cardiovascular disease observed in obesity. In addition, plasma levels of C-reactive peptide (CRP) increase with fat mass and decline with weight loss. 4Recently, CRP has been demonstrated to directly impair endothelium-dependent vasodilation, 5 and it is also known to be predictive of increased cardiovascular events in patients with other risk factors or with vascular disease. 6besity is also known to reduce vascular compliance. 7An increase in vascular stiffness has long-term adverse effects on the cardiovascular system by increasing impedance to blood flow and thereby increasing cardiovascular work and contributing to the development of left ventricular hypertrophy. Traditional risk factors are associated with vascular stiffness, and vascular stiffness is associated with an increased risk of cardiovascular events. 8 Leptin and Endothelial FunctionCuriously, plasma leptin levels were not correlated with flow-mediated vasodilation (FMVD). The investigators (incorrectly) concluded that ". . . the effect of leptin on arterial distensibility was independent of the short-term availability