FoxO1 suppresses Fgf21 during hepatic insulin resistance to impair peripheral glucose utilization and acute cold tolerance
Oliver Stöhr, Rongya Tao, Ji Miao, Kyle D. Copps, Morris F. White
Abstract
), a model of severe hepatic insulin resistance caused by deletion of hepatic Irs1 (insulin receptor substrate 1) and Irs2. Knockout of hepatic Foxo1 in LDKO mice or direct restoration of Fgf21 by adenoviral infection restored glucose utilization by BAT (brown adipose tissue) and skeletal muscle, normalized thermogenic gene expression in LDKO BAT, and corrected acute cold intolerance of LDKO mice. These studies highlight the Fgf21-dependent plasticity and importance of BAT function to metabolic health during hepatic insulin resistance.
Topics & Concepts
Insulin resistanceFOXO1PeripheralFGF21Internal medicineInsulinEndocrinologyMedicineBiologyCell biologySignal transductionReceptorProtein kinase BFibroblast growth factorFibroblast Growth Factor ResearchFOXO transcription factor regulationPancreatic function and diabetes