IN-VITRO LIPOLYTIC EFFECT OF LEPTIN ON MOUSE ADIPOCYTES - EVIDENCE FOR A POSSIBLE AUTOCRINE PARACRINE ROLE OF LEPTIN/

The present study has examined the effects of the adipocyte-derived ho rmone, leptin, on lipolysis in fat cells of different types of mice. E xposure to leptin (1.25 . 10(-6) M to 1.25 . 10(-12) M) increased (P < 0.01) the lipolytic activity of fat cells obtained from lean mice. A greater stimulation was observed when adipocytes from ob/ob mice were examined. Throughout the concentrations tested, the leptin-induced lip olysis observed in fat cells of lean animals was smaller than that obt ained in ob/ob mice. The maximal lipolytic effect in obese animals was observed with 10(-8) M of OB protein. The lipolytic activity followin g the addition of 1.25 . 10(-10) M to 1.25 . 10(-6) M was significantl y increased (P < 0.01) in ob/ob mice compared to lean animals. Adipocy tes from ob/ob mice responded in a dose-dependent manner to the OB pro tein, while the leptin-induced lipolysis observed in lean animals was dose-independent. In contrast to lean and ob/ob mice, leptin did not s timulate lipolysis in adipocytes from db/db mice, which have a mutatio n in the leptin receptor gene. These in vitro studies suggest an autoc rine/paracrine action of leptin on white fat cells and envisages the i nvolvement of the OB protein, not only in centrally mediated pathways, but also in physiological functions which take place peripherally. (C ) 1997 Academic Press.