| First Author | Duran-Sandoval D | Year | 2005 |
| Journal | J Biol Chem | Volume | 280 |
| Issue | 33 | Pages | 29971-9 |
| PubMed ID | 15899888 | Mgi Jnum | J:101042 |
| Mgi Id | MGI:3590426 | Doi | 10.1074/jbc.M501931200 |
| Citation | Duran-Sandoval D, et al. (2005) The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition. J Biol Chem 280(33):29971-9 |
| abstractText | 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. |
