Integrated Control of Hepatic Lipogenesis vs. Glucose Production Requires FoxO Transcription Factors

ABSTRACT: Insulin integrates hepatic glucose and lipid metabolism, directing nutrients to storage as glycogen and triglyceride. In type 2 diabetes, levels of the former are low and the latter are exaggerated, posing a pathophysiologic and therapeutic conundrum. A branching model1 of insulin signaling, with FoxO1 presiding over glucose production2-5 and Srebp–1c regulating lipogenesis,6-8 provides a potential explanation. Here we illustrate an alternative mechanism that integrates glucose production and lipogenesis under the unifying control of FoxO. Liver–specific ablation of three FoxOs (L–FoxO1,3,4) prevents the induction of glucose–6–phosphatase and the repression of glucokinase during fasting, thus increasing lipogenesis at the expense of glucose production. We document a similar pattern in the

ORGANISM(S): Mus musculus

SUBMITTER: Rebecca Haeusler 

PROVIDER: E-GEOD-60527 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress