Dual actions of figrowth factor 19 on lipid metabolism

Elevated triglyceride (TG) and cholesterol levels are risk factors for cardiovascular disease and are often as- sociated with diabetes and metabolic syndrome. Recent re- ports suggest that fi broblast growth factor (FGF)19 and FGF21 can dramatically improve metabolic dysfunction, in- cluding hyperglycemia, hypertriglyceridemia, and hyperc- holesterolemia. Due to their similar receptor specifi cities and co-receptor requirements, FGF19 and FGF21 share many common properties and have been thought to be in- terchangeable in metabolic regulation. Here we directly compared how pharmacological administration of recombi- nant FGF19 or FGF21 proteins affect metabolism in B6.V - Lep ob /J leptin-defi cient mice. FGF19 and FGF21 equally improved glucose parameters; however, we observed in- creased serum TG and cholesterol levels after treatment with FGF19 but not with FGF21. Increases in serum TGs were also observed after a 4-day treatment with FGF19 in C57BL6/J mice on a high-fat diet. This is in contrast to many literature reports that showed signifi cant improvements in hyperlipidemia after chronic treatment with FGF19 or FGF21 in high-fat diet models. We propose that FGF19 has lipid-raising and lipid-lowering actions mediated through different FGF receptors and target tissues, and the results described here provide a potential mechanism that may ex- plain the inconsistency in the reported effects of FGF19 on lipid metabolism. —Wu, X., H. Ge, H. Baribault, J. Gupte J. Weiszmann, B. Lemon, J. Gardner, P. Fordstrom, J. Tang, M. Zhou, M. Wang, and Y. Li. Dual actions of figrowth factor 19 on lipid metabolism. J. Lipid Res. 2013. 54: 325-332.