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 hormone, leptin, on lipolysis in fat cells of different types of mice. Exposure 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 lipolysis observed in fat cells of lean animals was smaller than that obtained in ob/ob mice. The maximal lipolytic effect in obese animals was observed with 10(-8) M of OB protein. The lipolytic activity following the addition of 1.25.10(-10) M to 1.25.10(-6) M was significantly increased (P < 0.01) in ob/ob mice compared to lean animals. Adipocytes from ob/ob mice responded in a dose-dependent manner to the OB protein, while the leptin-induced lipolysis observed in lean animals was dose-independent. In contrast to lean and ob/ob mice, leptin did not stimulate lipolysis in adipocytes from db/db mice, which have a mutation in the leptin receptor gene. These in vitro studies suggest an autocrine/paracrine action of leptin on white fat cells and envisages the involvement of the OB protein, not only in centrally mediated pathways, but also in physiological functions which take place peripherally.