Transcriptional Regulation of De Novo Lipogenesis in Liver

The liver is one of the main metabolic organs where de novo lipogenesis (DNL) takes place. DNL in the liver is tightly controlled by insulin and other metabolic hormones, as well as the availability of substrate, i.e., glucose level. In the positive energy balance, high concentration of glucose stimulates insulin secretion, activates ChREBP, and at the same time, provides substrate, which facilitate DNL in the liver. Accurate regulation of lipid levels is critical for cellular and organismal homeostasis, while deregulations in the lipogenic pathway are associated with diverse metabolic syndromes. This chapter will first introduce our current understanding about the DNL regulation by insulin-SREBP-1c pathway and ChREBP pathway, as well as other factors, including PPARγ, AMPK, SIRT1, circadian clock, ER stress and inflammation. At last, we will discuss the deregulation of DNL in metabolic syndromes and cancer, and potential targets for therapy.