INSULIN STIMULATES BOTH LEPTIN SECRETION AND PRODUCTION BY RAT WHITE ADIPOSE-TISSUE

Leptin, the peptide encoded by the obese gene, is secreted by adipose cells and plays a role in regulating food intake, energy expenditure, and adiposity. Because earlier studies suggested that insulin increase s the expression of leptin, we investigated the effect of insulin on l eptin secretion by adipose tissue. Epididymal fat pads were incubated in vitro in the presence or absence of insulin over a 4-h time course. Insulin increased leptin secretion by about 80% at all time points st udied. After 10 min of insulin treatment, the amount of tissue-associa ted leptin was lower in insulin-stimulated tissue, presumably due to t he increased secretion. At later times, bath tissue-associated leptin and total leptin production were higher in insulin-treated tissue. In untreated, isolated adipose cells, immunostaining of leptin was detect ed in the endoplasmic reticulum by confocal microscopy. After insulin treatment, there were two populations of cells. In many cells, leptin staining became fainter and was restricted to a narrow band near the p lasma membrane. However, in other cells the leptin-staining pattern wa s unchanged. Leptin did not colocalize with GLUT4, the glucose transpo rter isoform found primarily in insulin-responsive cells, in either ba sal or insulin-stimulated adipose cells. In this study, insulin increa sed both secretion and production of leptin by adipose tissue fragment s. Interestingly, insulin appeared to stimulate the transport of lepti n from the endoplasmic reticulum rather than acting on a pool of regul ated secretory vesicles.