Submitted by Hei Sook Sul on
Fatty acid synthase (FAS) is a principal enzyme in the regulation of lipogenesis. The synthesis of fatty acids is an energy expensive process and so the transcription of FAS is tightly regulated by an organism's nutritional state. FAS transcription is low during fasting and increases drastically upon refeeding. The concentration of insulin in circulation parallels that of metabolic substrates and is largely responsible for the increase in FAS transcription upon feeding. We have identified USF1 as a critical component of lipogenic gene transcription and found that its binding to the FAS promoter is required for FAS transcription. Furthermore, we identifed several other transcription factors and co-regulators that interact with USF1 for transcription of lipogenic genes in the presence of insulin and upon refeeding. Recently, we identified a histone demethylase that interacts with USF1 and are working to characterize this interaction and elucidate how this histone demethylase is regulated by fasting/refeeding. This work will provide an improved understanding of the epigenetic regulation of lipogenesis and may reveal new therapeutic targets for the treatment of obesity, hepatosteatosis, or insulin resistance.