Endothelin-1 stimulates leptin production in adipocytes

Leptin is an adipocyte-derived hormone that regulates body fat stores and feeding behavior. In an effort to identify endogenous diffusible modulators of leptin production, we found that endothelin-1 (ET-1) up-regulates leptin expression in adipocytes. ET-1 is as potent and efficacious as insulin in stimulating leptin production in two different adipocyte cell lines. Endothelins stimulate leptin production via the endothelin-A receptor (ETA), as judged by a potency rank order of ET-1 >> ET-3. We detected expression of ETA but not ETB in both cell lines by Northern blot analysis. In addition, the ETA-selective antagonist FR139317 inhibited ET-1-induced leptin expression more potently than did the ETB-selective antagonist BQ788. ET-1 and insulin positively interact with each other in increasing leptin production in adipocytes. In primary mouse white fat cells, we detected expression of both ETA and ETB by Northern blot and in situ hybridization analyses. We conclude that ET-1 stimulates leptin production via the ETA receptor in cultured adipocytes.