PSXIII-41 Fibroblast growth factor 21 promotes lipid oxidation and transportation while inhibits lipogenesis via AMP-activated protein kinase signaling pathway in bovine hepatocytes

Abstract

Abstract Background: Fibroblast growth factor 21 (FGF21) plays essential roles in the regulation of whole body energy metabolism. However, it is not entirely clear for dairy cows whether FGF21 activates AMPK signaling pathway and what will be affected for lipid metabolism in bovine hepatocytes. Methods: Bovine hepatocytes were isolated from caudate lobes by using three-step of perfusion and collagenase digestion method. The accumulation of TG and the secretion of VLDL were examined in hepatocytes and supernatant, respectively. The expressions of the metabolic key factors were detected by Real-time PCR and Western Blot.Results: The 4th hour is the optimal time that FGF21 activates AMPK. FGF21 has significant dose-dependent inhibition of TG in bovine hepatocytes; and high concentration (1800 pg/mL) significantly promoted VLDL secretion at 4 h. The protein expression of APOB 100, APOE and MTTP, which are components of VLDL, were stimulated by FGF21, and all the mRNA expression reached the peak point (P < 0.01) at medium concentration (900 pg/mL). Interestingly, the proteins associated with lipid transportation were promoted too, such as LDLR, CD36, L-FABP. To some extent, meanwhile, it could be observed that some genes regulating lipid oxidation were strengthened following FGF21 treatment. In detail, ACOX1 and SIRT1 were very sensitive to the concentration of FGF21, showing remarkable difference at low concentration (P < 0.01); PGC-α, PPAR-α and CPT-1 showed significant changes at 900 pg/mL (P < 0.01); CPT-2 required a higher concentration to achieve significant enhancement. However, the results had a negative impact on lipogenesis. SREBP1c, ACC, FASN and ACLY were inhibited after treatment with low or medium doses of FGF21 (P < 0.01). Conclusion: FGF21 can promote lipid oxidation and transport, while inhibit lipid synthesis via activating AMPK signalling pathway in primary hepatocytes of dairy cows, thereby participation in the adaptive regulation of energy metabolism.