Regulation of leptin production in humans

Serum levels of the adipocyte hormone leptin are increased in proportion to body fat stores as a result of increased production in enlarged fat cells from obese subjects. In vitro studies indicate that insulin and glucocortic oids work directly on adipose tissue to upregulate in a synergistic manner leptin mRNA levels and rates of leptin secretion in human adipose tissue ov er the long term. Thus, the increased leptin expression observed in obesity could result from the chronic hyperinsulinemia and increased cortisol turn over. Superimposed upon the long-term regulation, nutritional status can in fluence serum leptin over the short term, independent of adiposity. Fasting leads to a gradual decline in serum leptin that is probably attributable t o the decline in insulin and the ability of catecholamines to decrease lept in expression, as observed in both in vivo and in vitro studies. In additio n, increases in serum leptin occur similar to4-7 h after meals. Increasing evidence indicates that insulin, in concert with permissive effects of cort isol, can increase serum leptin over this time frame and likely contributes to meal-induced increases in serum leptin. Further research is required to elucidate the cellular and molecular mechanisms underlying short- and long -term nutritional and hormonal regulation of leptin production and secretio n.