LXRα Activity on Lipogenic and Reverse Cholesterol Tansport Genes is Differentially Regulated by Soy Protein Isoflavones

Soy protein regulates cholesterol and fatty acid metabolism via the liver X alpha‐receptor (LXRα). Soy isoflavones do not interact directly to regulate the expression of lipogenesis and reverse cholesterol transport genes. However, it is not know whether isoflavones can modulate the expression of these genes indirectly such as dithiolethiones that transactivate LXRα activity. With this purpose, we analyze the effects of the isoflavones genistein and daidzein in primary cultured hepatocytes stimulated with or without the synthetic ligand of LXRα, T0901317. Incubation of hepatocytes with T0901317 increased significantly FAS, ACC, SCD1, ABCA1, and ABCG5 mRNA concentration with respect to the control group. Incubation of hepatocytes with either genistein or daidzein did not show an effect on the expression of these genes. Interestingly, hepatocytes stimulated with T0901317 with one of the isoflavones, significantly reduced the stimulating effect of the synthetic ligand of LXRα on lipogenic genes. However, this treatment increased the expression of ABCG5 reverse cholesterol transporter. The inhibitory or stimulatory effects of isoflavones on cells stimulated with T0901317, suggest that isoflavones may regulate indirectly the activity of LXRα differentially on lipogenic and reverse cholesterol transport genes. Supported by CONACYT Grant No 84786 (to O.G)