A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response.

ABSTRACT: While the physiological benefits of the fibroblast growth factor 21 (FGF21) hepatokine are documented in response to fasting, little information is available on Fgf21 regulation in a glucose-overload context. We report that peroxisome-proliferator-activated receptor α (PPARα), a nuclear receptor of the fasting response, is required with the carbohydrate-sensitive transcription factor carbohydrate-responsive element-binding protein (ChREBP) to balance FGF21 glucose response. Microarray analysis indicated that only a few hepatic genes respond to fasting and glucose similarly to Fgf21. Glucose-challenged Chrebp^-/- mice exhibit a marked reduction in FGF21 production, a decrease that was rescued by re-expression of an active ChREBP isoform in the liver of Chrebp^-/- mice. U

SUBMITTER: Iroz A 

PROVIDER: S-EPMC5643524 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature