| First Author | Fisher FM | Year | 2011 |
| Journal | Endocrinology | Volume | 152 |
| Issue | 8 | Pages | 2996-3004 |
| PubMed ID | 21712364 | Mgi Jnum | J:174843 |
| Mgi Id | MGI:5141328 | Doi | 10.1210/en.2011-0281 |
| Citation | Fisher FM, et al. (2011) Integrated Regulation of Hepatic Metabolism by Fibroblast Growth Factor 21 (FGF21) in Vivo. Endocrinology 152(8):2996-3004 |
| abstractText | Fibroblast growth factor (FGF21) plays an important role in regulating hepatic oxidation of fatty acids and gluconeogenesis in response to fasting and during consumption of a ketogenic diet. However, the metabolic pathways through which FGF21 regulates hepatic function are not well defined. To identify the effects of FGF21 on the liver in vivo, we administered FGF21 to mice and analyzed acute effects on signaling and gene expression. We found that FGF21 acts directly on the liver to stimulate phosphorylation of fibroblast growth factor receptor substrate 2 and ERK1/2. Acute FGF21 treatment induced hepatic expression of key regulators of gluconeogenesis, lipid metabolism, and ketogenesis including glucose-6-phosphatase, phosphoenol pyruvate carboxykinase, 3-hydroxybutyrate dehydrogenase type 1, and carnitine palmitoyltransferase 1alpha. In addition, injection of FGF21 was associated with decreased circulating insulin and free fatty acid levels. FGF21 treatment induced mRNA and protein expression of peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha), suggesting that PGC-1alpha may play a role in regulating FGF21 action. However, studies using mice with liver-specific ablation of PGC-1alpha revealed the same regulation of gluconeogenic gene expression by FGF21 as seen in wild-type mice, indicating that PGC-1alpha is not necessary for the effect of FGF21 on glucose metabolism. These data demonstrate that FGF21 acts directly on the liver to modulate hepatic metabolism. The direct effects we examined are not dependent on PGC-1alpha. In addition, FGF21 treatment is associated with decreased serum insulin levels that my affect hepatic function. |
