Endothelin-1 stimulates leptin production in adipocytes

Leptin is an adipocyte-derived hormone that regulates body fat stores and f eeding 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. Endoth elins stimulate leptin production via the endothelin-A receptor (ETA), as j udged by a potency rank order of ET-1 >> ET-3. We detected expression of ET A but not ETB in both cell lines by Northern blot analysis. In addition, th e ETA-selective antagonist FR139317 inhibited ET-1-induced leptin expressio n more potently than did the ETB-selective antagonist BQ788. ET-1 and insul in positively interact with each other in increasing leptin production in a dipocytes. In primary mouse white fat cells, we detected expression of both ETA and ETB by Northern blot and in situ hybridization analyses. We conclu de that ET-1 stimulates leptin production via the ETA receptor in cultured adipocytes.