ChRESP and LXRα mediate synergistically lipogenesis induced by glucose in porcine adipocytes

Glucose is a substrate for fatty acid synthesis, and induces lipogenesis and expressions of lipogenic genes. It was proposed that transcriptional factor ChREBP, LXR alpha and 5REBP-1c are key mediators in lipogenesis induced by glucose, however the underlying mechanism remains unclear in porcine adipocytes. In this study, glucose stimulated lipogenesis and expressions of ChREBP, LXR alpha, SREBP-1c and lipogenic genes FAS and ACC1 in primary porcine adipocytes. When ChREBP expression was knocked down by RNAi, lipogenesis and FAS and ACC1 expressions decreased significantly, and lipogenesis induced by glucose decreased by 75.6%, whereas neither the basal expressions under glucose-free nor glucose induced expressions of LXR alpha and SREBP-1 c were evidently affected, suggesting that ChREBP was a main mediator of lipogenesis stimulated by glucose. Glucose promoted LXR alpha gene expression, and activation of LXR alpha by T0901317 increased SREBP-1c expression and enhanced the stimulation of glucose on lipogenesis, but this stimulatory effect of LXR alpha depended on glucose. Activated Ma stimulated lipogenesis and ChREBP mRNA expression, which was much lower than that elevated by glucose, and was markedly lower in ChREBP-silencing than in unperturbed adipocytes. SREBP-1c activation blocked by fatostatin markedly decreased lipogenesis and expressions of FAS and ACC1 induced by glucose. Lipogenesis and lipogenic gene expression stimulated by LXR alpha activation were attenuated by fatostatin, however there was still a slightly increase in ChREBP-silencing adipocytes. These dates suggested that LXR alpha could directly or through 5REBP-1c mediate the lipogenesis induced by glucose. Together, glucose induced lipogenesis and lipogenic gene expressions directly through ChREBP, and directly through LXR alpha or via SREBP-1c. (C) 2015 Elsevier B.V. All rights reserved.