| First Author | Potthoff MJ | Year | 2011 |
| Journal | Cell Metab | Volume | 13 |
| Issue | 6 | Pages | 729-38 |
| PubMed ID | 21641554 | Mgi Jnum | J:176084 |
| Mgi Id | MGI:5288293 | Doi | 10.1016/j.cmet.2011.03.019 |
| Citation | Potthoff MJ, et al. (2011) FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1alpha pathway. Cell Metab 13(6):729-38 |
| abstractText | Regulation of hepatic carbohydrate homeostasis is crucial for maintaining energy balance in the face of fluctuating nutrient availability. Here, we show that the hormone fibroblast growth factor 15/19 (FGF15/19), which is released postprandially from the small intestine, inhibits hepatic gluconeogenesis, like insulin. However, unlike insulin, which peaks in serum 15 min after feeding, FGF15/19 expression peaks approximately 45 min later, when bile acid concentrations increase in the small intestine. FGF15/19 blocks the expression of genes involved in gluconeogenesis through a mechanism involving the dephosphorylation and inactivation of the transcription factor cAMP regulatory element-binding protein (CREB). This in turn blunts expression of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and other genes involved in hepatic metabolism. Overexpression of PGC-1alpha blocks the inhibitory effect of FGF15/19 on gluconeogenic gene expression. These results demonstrate that FGF15/19 works subsequent to insulin as a postprandial regulator of hepatic carbohydrate homeostasis. |
