Genistein affects lipogenesis and lipolysis in isolated rat adipocytes.
Genistein is a phytoestrogen 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 degrees C with Krebs-Ringer buffer, 90 min) with genistein (0.01, 0.3, 0.6 and 1 mM) clearly restricted (1 nM) [U-14C]glucose conversion to total lipids in the absence and presence of insulin. When [14C]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 esterification. 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 1 mM) augmented basal lipolysis in adipocytes. This process was strongly restricted by insulin (1 microM) and H-89 (an inhibitor of protein kinase A; 50 microM) and seems to be primarily due to the inhibitory action of the phytoestrogen on cAMP phosphodiesterase in adipocytes. Genistein at the smallest concentration (0.01 mM) augmented epinephrine-stimulated (1 microM) lipolysis but failed to potentiate lipolysis induced by forskolin (1 microM) or dibutyryl-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 phytoestrogen 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.
Szkudelska
K
K
Department of Animal Physiology and Biochemistry, University of Agriculture, 60-637 Wołyńska 35, Poznan, Poland. kakandu@jay.au.poznan.pl
Nogowski
L
L
Szkudelski
T
T
D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004837:Epinephrine / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007529:Isoflavones; D008055:Lipids / Q000096:biosynthesis*; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D048789:Phytoestrogens; D028321:Plant Preparations; D051381:Rats; D017208:Rats, Wistar; D002787:Sterol Esterase / Q000037:antagonists & inhibitors
D004968:Estrogens, Non-Steroidal; D007529:Isoflavones; D008055:Lipids; D048789:Phytoestrogens; D028321:Plant Preparations; D005576:Colforsin; D004958:Estradiol; D003994:Bucladesine; D019833:Genistein; D017868:Cyclic AMP-Dependent Protein Kinases; D002787:Sterol Esterase; D004837:Epinephrine