In VitroLipolytic Effect of Leptin on Mouse Adipocytes: Evidence for a Possible Autocrine/Paracrine Role of Leptin

Abstract

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 (1.25·10⁻⁶M to 1.25·10⁻¹²M) increased (P< 0.01) the lipolytic activity of fat cells obtained from lean mice. A greater stimulation was observed when adipocytes fromob/obmice were examined. Throughout the concentrations tested, the leptin-induced lipolysis observed in fat cells of lean animals was smaller than that obtained inob/obmice. The maximal lipolytic effect in obese animals was observed with 10⁻⁸M of OB protein. The lipolytic activity following the addition of 1.25·10⁻¹⁰M to 1.25·10⁻⁶M was significantly increased (P< 0.01) inob/obmice compared to lean animals. Adipocytes fromob/obmice 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 andob/obmice, leptin did not stimulate lipolysis in adipocytes fromdb/dbmice, which have a mutation in the leptin receptor gene. Thesein vitrostudies 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.