Regulatory Roles of FoxO Transcription Factors in Metabolism

Forkhead Box O (FoxO) transcription factors play an important role in modulating metabolic functions. FoxOs,which are conserved among species and are regulated by the insulin signaling pathway,are usually expressed in insulin-sensitive tissues,including the liver,pancreas,skeletal muscle and gastrointestinal (GI) tract. During calorie restriction or starvation, FoxOs are predominantly localized to the cell nucleus where they activate transcription to increase hepatic gluconeogenesis,decrease insulin secretion,increase food intake and stimulate skeletal muscle degradation to supply substrates for gluconeogenesis. In insulin re-sistance or excess calorie supply,FoxOs are inactivated and lose their transcriptional activity. FoxOs also regulate the development of insulin-sensitive tissues by controlling cell differentiation,proliferation and survival. In this paper,we review the metabolic and cell cyclerelated genes controlled by FoxOs in insulin-sensitive tissues as well as their metabolic effects. Further studies into the roles of FoxOs,and the underlying mechanisms,in insulin-sensitive tissues will strengthen our understanding about tissue development and energy metabolism.