Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective

Transcription of enzymes involved in FA and TAG synthesis is coordinately induced in lipogenic tissues by feeding and insulin treatment. The three major transcription factors involved are USF, SREBP-1c, and LXRα. New insights into the insulin-signaling pathway(s) that control(s) lipogenic gene transcription via these factors have recently been revealed. Dephosphorylation/activation of DNA-PK by PP1 causes phosphorylation of USF that in turn recruits P/CAF to be acetylated for transcriptional activation. SREBP-1c can be induced by mTORC1, bifurcating lipogenesis from AKT-activated gluconeogenesis. LXRα may serve as a glucose sensor and, along with ChREBP, may activate lipogenic genes in the fed state. Dysregulation of FA and TAG metabolism often contributes to metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Transcription factors and signaling molecules involved in transcriptional activation of FA and TAG synthesis represent attractive targets for the prevention and treatment of metabolic diseases.