Genistein affects lipogenesis and lipolysis in isolated rat adipocytes

Genistein is a photoestrogen found in several plants eaten by humans and food-producing animals and exerting a wide spectrum of biological activity. In this experiment. the: impact of genistein on lipogenesis and lipolysis was studied in isolated rat adipocytes. Incubation of the cells (10(6) cells/ml in plastic tubes at 37 degreesC with Krebs-Ringer buffer, 90 min) with genistein (0.01. 0.3. 0.6 and mM) clearly restricted (1 nM) [U-C-14]glucose: conversion to total lipids in the absence and presence of insulin. When [C-14]acetate was used as the substrate for lipogenesis, genistein (0.01. 0.1 and 1 mM) exerted a similar effect. Thus, the anti-lipogenetic action of genistein may be an effect not only of alteration in glucose transport and metabolism, but this phytoestrogen can also restrict the fatty acids synthesis and/or their estrification. Incubation of adipocytes with estradiol at the same concentrations also resulted in restriction of lipogenesis. but the effect was less marked. Genistein (0.1 and mM) augmented basal lipolysis in adipocytes. This process was strongly restricted by insulin (1 muM) and H-89 (an inhibitor of protein kinase A: 50 muM) and seems to be primarily due to the inhibitory action of the phytoestrogren on cAMP phosphodiesterase in adipocytes. Genistein at the smallest concentration (0.01 mM) augmented epinephrine-stimulated (1 mM) lipolysis but failed to potentiate lipolysis induced by forskolin (1 muM) or dibutylyl-cAMP (1 mM). These results suggest genistein action on the lipolytic pathways before activation of adenylate cyclase. The restriction of lipolysis stimulated by several lipolytic agents epinephrine, forskolin and dibutyryl-cAMP were observed when adipocytes were incubated with genistein at highest concentrations (0.1 and 1 mM). These results prove the inhibitory action of this phyestrogen on the final steps of the lipolytic cascade, i.e. on protein kinase A or hormone sensitive lipase. Estradiol, added to the incubation medium. did not affect lipolysis. It can be concluded that genistein significantly affects lipogenesis and lipolysis in isolated rat adipocytes. (C) 2001 Elsevier Science Ltd. All rights reserved.