| First Author | Iroz A | Year | 2017 |
| Journal | Cell Rep | Volume | 21 |
| Issue | 2 | Pages | 403-416 |
| PubMed ID | 29020627 | Mgi Jnum | J:262506 |
| Mgi Id | MGI:6163647 | Doi | 10.1016/j.celrep.2017.09.065 |
| Citation | Iroz A, et al. (2017) A Specific ChREBP and PPARalpha Cross-Talk Is Required for the Glucose-Mediated FGF21 Response. Cell Rep 21(2):403-416 |
| abstractText | 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 alpha (PPARalpha), 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. Unexpectedly, carbohydrate challenge of hepatic Pparalpha knockout mice also demonstrated a PPARalpha-dependent glucose response for Fgf21 that was associated with an increased sucrose preference. This blunted response was due to decreased Fgf21 promoter accessibility and diminished ChREBP binding onto Fgf21 carbohydrate-responsive element (ChoRE) in hepatocytes lacking PPARalpha. Our study reports that PPARalpha is required for the ChREBP-induced glucose response of FGF21. |
