Genistein affects lipogenesis and lipolysis in isolated rat adipocytes

Genistein is a photoestrogen found in several plants eaten by humans and fo od-producing animals and exerting a wide spectrum of biological activity. I n this experiment. the: impact of genistein on lipogenesis and lipolysis wa s 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 g enistein (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 g enistein may be an effect not only of alteration in glucose transport and m etabolism, but this phytoestrogen can also restrict the fatty acids synthes is and/or their estrification. Incubation of adipocytes with estradiol at t he same concentrations also resulted in restriction of lipogenesis. but the effect was less marked. Genistein (0.1 and mM) augmented basal lipolysis i n 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 du e 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 sugges t genistein action on the lipolytic pathways before activation of adenylate cyclase. The restriction of lipolysis stimulated by several lipolytic agen ts epinephrine, forskolin and dibutyryl-cAMP were observed when adipocytes were incubated with genistein at highest concentrations (0.1 and 1 mM). The se results prove the inhibitory action of this phyestrogen on the final ste ps 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 ri ghts reserved.