Transcriptional Control of Hepatic Lipid Metabolism by SREBP and ChREBP

The liver is a central organ that controls systemic energy homeostasis and nutrient metabolism. Dietary carbohydrates and lipids, and fatty acids derived from adipose tissue are delivered to the liver, and utilized for gluconeogenesis, lipogenesis, and ketogenesis, which are tightly regulated by hormonal and neural signals. Hepatic lipogenesis is activated primarily by insulin that is secreted from the pancreas after a high-carbohydrate meal. Sterol regulatory element binding protein-1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP) are major transcriptional regulators that induce key lipogenic enzymes to promote lipogenesis in the liver. Sterol regulatory element binding protein-1c is activated by insulin through complex signaling cascades that control SREBP-1c at both transcriptional and posttranslational levels. Carbohydrate-responsive element-binding protein is activated by glucose independently of insulin. Here, the authors attempt to summarize the current understanding of the molecular mechanism for the transcriptional regulation of hepatic lipogenesis, focusing on recent studies that explore the signaling pathways controlling SREBPs and ChREBP.