The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition
The liver plays a central role in the control of blood glucose homeostasis by maintaining a balance between glucose production and utilization. The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor. Hepatic FXR expression is regulated by glucose and insulin. Here we identify a role for FXR in the control of hepatic carbohydrate metabolism. When submitted to a controlled fasting-refeeding schedule, FXR(-/-) mice displayed an accelerated response to high carbohydrate refeeding with an accelerated induction of glycolytic and lipogenic genes and a more pronounced repression of gluconeogenic genes. Plasma insulin and glucose levels were lower in FXR(-/-) mice upon refeeding the high-carbohydrate diet. These alterations were paralleled by decreased hepatic glycogen content. Hepatic insulin sensitivity was unchanged in FXR(-/-) mice. Treatment of isolated primary hepatocytes with a synthetic FXR agonist attenuated glucose-induced mRNA expression as well as promoter activity of L-type pyruvate kinase, acetyl-CoA carboxylase 1, and Spot14. Moreover, activated FXR interfered negatively with the carbohydrate response elements regions. These results identify a novel role for FXR as a modulator of hepatic carbohydrate metabolism.
| Medienart: |
Artikel |
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| Erscheinungsjahr: |
2005 |
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| Erschienen: |
2005 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:280 |
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| Enthalten in: |
The Journal of biological chemistry - 280(2005), 33 vom: 19. Aug., Seite 29971-9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Duran-Sandoval, Daniel [VerfasserIn] |
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| Themen: |
0C5V0MRU6P |
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| Anmerkungen: |
Date Completed 22.09.2005 Date Revised 09.02.2021 published: Print-Electronic Citation Status MEDLINE |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM155433946 |
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| 100 | 1 | |a Duran-Sandoval, Daniel |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition |
| 264 | 1 | |c 2005 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 22.09.2005 | ||
| 500 | |a Date Revised 09.02.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a The liver plays a central role in the control of blood glucose homeostasis by maintaining a balance between glucose production and utilization. The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor. Hepatic FXR expression is regulated by glucose and insulin. Here we identify a role for FXR in the control of hepatic carbohydrate metabolism. When submitted to a controlled fasting-refeeding schedule, FXR(-/-) mice displayed an accelerated response to high carbohydrate refeeding with an accelerated induction of glycolytic and lipogenic genes and a more pronounced repression of gluconeogenic genes. Plasma insulin and glucose levels were lower in FXR(-/-) mice upon refeeding the high-carbohydrate diet. These alterations were paralleled by decreased hepatic glycogen content. Hepatic insulin sensitivity was unchanged in FXR(-/-) mice. Treatment of isolated primary hepatocytes with a synthetic FXR agonist attenuated glucose-induced mRNA expression as well as promoter activity of L-type pyruvate kinase, acetyl-CoA carboxylase 1, and Spot14. Moreover, activated FXR interfered negatively with the carbohydrate response elements regions. These results identify a novel role for FXR as a modulator of hepatic carbohydrate metabolism | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a DNA-Binding Proteins |2 NLM | |
| 650 | 7 | |a Lipids |2 NLM | |
| 650 | 7 | |a Receptors, Cytoplasmic and Nuclear |2 NLM | |
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| 650 | 7 | |a farnesoid X-activated receptor |2 NLM | |
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| 700 | 1 | |a Cariou, Bertrand |e verfasserin |4 aut | |
| 700 | 1 | |a Percevault, Fredéric |e verfasserin |4 aut | |
| 700 | 1 | |a Hennuyer, Nathalie |e verfasserin |4 aut | |
| 700 | 1 | |a Grefhorst, Aldo |e verfasserin |4 aut | |
| 700 | 1 | |a van Dijk, Theo H |e verfasserin |4 aut | |
| 700 | 1 | |a Gonzalez, Frank J |e verfasserin |4 aut | |
| 700 | 1 | |a Fruchart, Jean-Charles |e verfasserin |4 aut | |
| 700 | 1 | |a Kuipers, Folkert |e verfasserin |4 aut | |
| 700 | 1 | |a Staels, Bart |e verfasserin |4 aut | |
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