dc.contributor.authorIroz, Alison
dc.contributor.authorMontagner, Alexandra
dc.contributor.authorBenhamed, Fadila
dc.contributor.authorLevavasseur, Françoise
dc.contributor.authorPolizzi, Arnaud
dc.contributor.authorAnthony, Elodie
dc.contributor.authorRégnier, Marion
dc.contributor.authorFouché, Edwin
dc.contributor.authorLukowicz, Céline
dc.contributor.authorCauzac, Michèle
dc.contributor.authorTournier, Emilie
dc.contributor.authorDo-Cruzeiro, Marcio
dc.contributor.authorDaujat-Chavanieu, Martine
dc.contributor.authorGerbal-Chalouin, Sabine
dc.contributor.authorFauveau, Véronique
dc.contributor.authorMarmier, Solenne
dc.contributor.authorBurnol, Anne-Françoise
dc.contributor.authorGuilmeau, Sandra
dc.contributor.authorLippi, Yannick
dc.contributor.authorGirard, Jean
dc.contributor.authorWahli, Walter
dc.contributor.authorDentin, Renaud
dc.contributor.authorGuillou, Hervé
dc.contributor.authorPostic, Catherine
dc.identifier.citationIroz, A., Montagner, A., Benhamed, F., Levavasseur, F., Polizzi, A., Anthony, E., et al. (2017). A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response. Cell Reports, 21(2), 403-416.en_US
dc.description.abstractWhile 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. Unexpectedly, carbohydrate challenge of hepatic Pparα knockout mice also demonstrated a PPARα-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 PPARα. Our study reports that PPARα is required for the ChREBP-induced glucose response of FGF21.en_US
dc.format.extent15 p.en_US
dc.relation.ispartofseriesCell Reportsen_US
dc.rights© 2017 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).en_US
dc.titleA Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Responseen_US
dc.typeJournal Article
dc.contributor.schoolLee Kong Chian School of Medicineen_US
dc.description.versionPublished versionen_US

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