Molecular Mechanism of Obesity and Appetite Regulation

Role of Leptin

Abstract

Leptin is an adipocyte-derived blood-borne satiety factor that acts directly on the hypothalamus, thereby reducing food intake and increasing energy expenditure. Congenital leptin deficiency or leptin receptor gene mutations result in severe obesity and hypothalamic hypogonadism in rodents and humans. However, plasma leptin concentrations are mostly elevated in acquired obesity in proportion to the degree of adiposity, indicating the potential diagnostic role of leptin as a marker of adiposity. Transgenic overexpression of leptin, which increases plasma leptin to concentrations comparable with those in obese subjects, causes disappearance of lipid from adipose tissue in mice (transgenic skinny mice). The animals exhibit increased glucose metabolism and insulin sensitivity accompanied by increased insulin signaling for glucose disposal. They also show blood pressure elevation as a result of sympathetic activation. These findings have both pathophysiologic and therapeutic implications for leptin in several types of diabetes and obesity-related hypertension.