A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response
Summary: 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 rec...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-10-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124717313700 |
| _version_ | 1828393135008382976 |
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| author | Alison Iroz Alexandra Montagner Fadila Benhamed Françoise Levavasseur Arnaud Polizzi Elodie Anthony Marion Régnier Edwin Fouché Céline Lukowicz Michèle Cauzac Emilie Tournier Marcio Do-Cruzeiro Martine Daujat-Chavanieu Sabine Gerbal-Chalouin Véronique Fauveau Solenne Marmier Anne-Françoise Burnol Sandra Guilmeau Yannick Lippi Jean Girard Walter Wahli Renaud Dentin Hervé Guillou Catherine Postic |
| author_facet | Alison Iroz Alexandra Montagner Fadila Benhamed Françoise Levavasseur Arnaud Polizzi Elodie Anthony Marion Régnier Edwin Fouché Céline Lukowicz Michèle Cauzac Emilie Tournier Marcio Do-Cruzeiro Martine Daujat-Chavanieu Sabine Gerbal-Chalouin Véronique Fauveau Solenne Marmier Anne-Françoise Burnol Sandra Guilmeau Yannick Lippi Jean Girard Walter Wahli Renaud Dentin Hervé Guillou Catherine Postic |
| author_sort | Alison Iroz |
| collection | DOAJ |
| description | Summary: 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. 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. : FGF21 is a hepatokine with beneficial metabolic effects, including control of sucrose preference. Iroz et al. demonstrate that Fgf21 is a unique hepatic gene inducible by both fasting and glucose signals and that the transcription factors PPARα and ChREBP both regulate the endocrine control of sugar intake by hepatic FGF21. Keywords: ChREBP, PPARα, FGF21, glucose intake, sucrose preference |
| first_indexed | 2024-12-10T07:33:07Z |
| format | Article |
| id | doaj.art-27cfd3a0fbcd4dd49659cb793fec8873 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-10T07:33:07Z |
| publishDate | 2017-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-27cfd3a0fbcd4dd49659cb793fec88732022-12-22T01:57:30ZengElsevierCell Reports2211-12472017-10-01212403416A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 ResponseAlison Iroz0Alexandra Montagner1Fadila Benhamed2Françoise Levavasseur3Arnaud Polizzi4Elodie Anthony5Marion Régnier6Edwin Fouché7Céline Lukowicz8Michèle Cauzac9Emilie Tournier10Marcio Do-Cruzeiro11Martine Daujat-Chavanieu12Sabine Gerbal-Chalouin13Véronique Fauveau14Solenne Marmier15Anne-Françoise Burnol16Sandra Guilmeau17Yannick Lippi18Jean Girard19Walter Wahli20Renaud Dentin21Hervé Guillou22Catherine Postic23INSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceToxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceToxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceToxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, FranceToxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, FranceToxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceINSERM, U1183, Institute for Regenerative Medicine and Biotherapy, Montpellier, France; Université de Montpellier, UMR 1183, Montpellier, France; CHU Montpellier, Institute for Regenerative Medicine and Biotherapy, Montpellier, FranceINSERM, U1183, Institute for Regenerative Medicine and Biotherapy, Montpellier, France; Université de Montpellier, UMR 1183, Montpellier, France; CHU Montpellier, Institute for Regenerative Medicine and Biotherapy, Montpellier, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceToxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, FranceINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, FranceToxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, France; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore; Center for Integrative Genomics, University of Lausanne, Genopode Building, Lausanne 1015, SwitzerlandINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, France; Corresponding authorToxalim, Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse 31027, France; Corresponding authorINSERM U1016, Institut Cochin, Paris 75014, France; CNRS UMR 8104, Paris 75014, France; University of Paris Descartes, Sorbonne Paris Cité, Paris 75005, France; Corresponding authorSummary: 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. 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. : FGF21 is a hepatokine with beneficial metabolic effects, including control of sucrose preference. Iroz et al. demonstrate that Fgf21 is a unique hepatic gene inducible by both fasting and glucose signals and that the transcription factors PPARα and ChREBP both regulate the endocrine control of sugar intake by hepatic FGF21. Keywords: ChREBP, PPARα, FGF21, glucose intake, sucrose preferencehttp://www.sciencedirect.com/science/article/pii/S2211124717313700 |
| spellingShingle | Alison Iroz Alexandra Montagner Fadila Benhamed Françoise Levavasseur Arnaud Polizzi Elodie Anthony Marion Régnier Edwin Fouché Céline Lukowicz Michèle Cauzac Emilie Tournier Marcio Do-Cruzeiro Martine Daujat-Chavanieu Sabine Gerbal-Chalouin Véronique Fauveau Solenne Marmier Anne-Françoise Burnol Sandra Guilmeau Yannick Lippi Jean Girard Walter Wahli Renaud Dentin Hervé Guillou Catherine Postic A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response Cell Reports |
| title | A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response |
| title_full | A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response |
| title_fullStr | A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response |
| title_full_unstemmed | A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response |
| title_short | A Specific ChREBP and PPARα Cross-Talk Is Required for the Glucose-Mediated FGF21 Response |
| title_sort | specific chrebp and pparα cross talk is required for the glucose mediated fgf21 response |
| url | http://www.sciencedirect.com/science/article/pii/S2211124717313700 |
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