Obesity and Cardiovascular Disease (Beckman Conference‪)‬

Obesity plays a pivotal role in the pathophysiology of metabolic and cardiovascular disease (1-13). These disorders include impaired glucose tolerance, Type 2 diabetes, hypertension, and dyslipidemia. Obesity, defined as excessive storage of energy in the form of fat, has adverse effects on other diseases, such as certain cancers, which contribute to increased morbidity and mortality in our increasingly overweight society. If obesity is defined as a body mass index of 20% above the desirable index (approximately a body mass index of 27 kg/[m.sup.2]), ~34 million adult Americans can be considered obese (12). Increasing related adiposity as a function of increasing age (14-16) also contributes to the increase in diabetes and hypertension with aging in Westernized, industrialized societies. The cause of obesity is unknown, but abnormalities of leptin homeostasis have been proposed to increase the propensity to obesity (17). Leptin is a 16-kDa polypeptide hormone synthesized and released by the adipose tissue in proportion to the amount of triglyceride stores (17). Development of obesity in some rodent models is related to mutations in leptin or the leptin receptor. Furthermore, administration of leptin to obese rats lacking leptin normalizes body weight, metabolism, and the regulation of the hypothalamic-pituitary axis (17). However, most obese persons have no mutations in leptin or the leptin receptor. Indeed, they have increased leptin proportionate to their adiposity (17). Because the expected increase in leptin concentration would be expected to decrease appetite and increase thermogenesis, some obese persons may be resistant to their high endogenous leptin concentrations. Thus, the clinical utility of measuring serum leptin concentrations is unknown. Clinical trials are in progress to evaluate the effects of administration of exogenous leptin or leptin analogs in an attempt to overcome the leptin resistance.