The Effect Of FGF21on Lipid Metabolism And Study On The Relationship Between FGF21and FoxA2in Obese Rats Induced By High Fat Diet

Obesity is mainly caused by imbalance of energy metabolism or triglycerideaccumulation due to the excessive intake of food. obesity is listed as the fifth mostserious risk factor and involved in many chronic diseases,so it has become a globalepidemic disease.Fibroblast growth factor21(FGF21) has been identified as an effective metabolicregulator of glucose and lipid homeostasis. It could promote ketogenesis, fatty acidsβoxidation and insulin secretion. As a deacetylase enzyme, Sirt1activates theexpression of downstream target by deacetylation. And FGF21enhances fatty acidsβoxidation and regulates mitochondrial activity through an AMPK/Sirt1/PGC-1αpathway.FoxA2is one of the member of forkhead box family, and has an important role onthe immune regulation, glucose and lipid metabolism and regulation of cell cycle. Thetranscriptional activity of PGC-1β could be repressed by acetylation reaction ofGCN5, and reversed by Sirt1.Furthermore, FoxA2could form a transcriptionalcoactivator complex with PGC-1β, thereby regulating the expression of ApoM and ApoB. It has been proved that FGF21activates Sirt1via AMPK to control fatty acidsβoxidation and mitochondrial activity. However, there is no report on FGF21regulatiom of glucose and lipid metabolism via FoxA2.The study detected the effects of different doses of FGF21on physiological andbiochemical indexes of DOI rat and the regulation pathway between FGF21andFoxA2by using Western blot, Real time-PCR, ELISA and IHC. The results indicatedthat accompanied with the dose increased, the regulatory effect of FGF21on the bodyweight, TG, LDL-C, HDL-C were strengthened significantly. Chronic FGF21treatment had a better effect on preventing obesity and the lipid metabolism. FGF21also dramatically upregulated the expression of Sirt1and FoxA2in a dosedependently manner.The results showed that FGF21reduced body weight, TG, LDL-C and increasedHDL-C in the DOI rat with a dose-dependent manner. Besides, using FGF21in the earlystage could prevent it obesity from getting worse. On the other hand, the result indicatedthat FoxA2, a transcription factor and regulator of energy metabolism was regulated byFGF21. By the pathway, AMPK/Sirt1/PGC-1β, in a dose-dependent manner. However,Further studies should be launched to investigate the roles of GCN5and PGC-1β inthis pathway as well as their relationship with FGF21.