Intrinsic site-specific differences in the expression of leptin in human adipocytes and its autocrine effects on glucose uptake

Leptin, the ob gene product of adipocytes, regulates body weight by actions on the satiety center in the hypothalamus, but it may also have peripheral effects on the metabolic actions of insulin. In human mature adipocytes is olated from omental (OM) and sc tissue, we found that leptin (10 and 100 ng /mL) significantly reduced insulin-mediated glucose uptake by 40% (P < 0.05 ). The effects were rapid and sustained. A U-shaped dose-response curve was obtained, and high leptin concentrations (>100 ng/mL) were without effect. Leptin did not affect basal glucose uptake in adipocytes and had no effect on insulin-stimulated glucose uptake in human preadipocytes. Because lepti n may thus have autocrine effects, we examined leptin production fi om OM a nd sc adipocytes. Western blotting of leptin from 96-h conditioned medium s howed greater leptin secretion from sc than OM adipocytes, with a ratio of 3.2 (SE +/- 0.3, P < 0.01). Long-term ceiling cultures were used to examine intrinsic differences in leptin expression under closely controlled condit ions. Confocal immunofluorescence microscopy of 12- to 16-day-old ceiling-c ultured adipocytes showed that sc adipocytes contained 3.4-fold more leptin (SE +/- 0.5, P < 0.01) than OM adipocytes, indicating an intrinsic site-sp ecific difference in leptin production. The autocrine effects of leptin to inhibit insulin-stimulated glucose uptake and subsequent lipogenesis in adi pose tissue may, therefore, be less in OM adipocytes and may play a role in determining visceral obesity.