Abstract
Objective To investigate the effects of fibroblast growth factor-21 (FGF-21) gene knockdown on the expression of hepatic glyconeogenesis-related genes in ApoE-/-mice and its mechanism.Methods Twenty-four 8-week-old male ApoE-/-mice were randomly divided into chow diet fed group(NC,n =6),chow diet+pAd-shFGF-21group(NF,n=6),high-fat diet fed group(HC,n=6),and high-fat diet+pAd-shFGF-21 group(HF,n=6).Mice were fed for 16 weeks.NC and HC groups injected with pAd-shGFP,however NF and HF groups were injected with pAd-shFGF-21 through the tail vein at the end of the 15th week.At the end of the 16th week,blood samples were collected for measurement of plasma glucose,insulin and lipid levels.Hepatic tissues were collected for measurement of mRNA and protein levels of glyconeogenesis-related genes and JAK2/STAT3 signaling pathway via real-time PCR and Western-blot,respectively.Results The fasting plasma glucose (FBG),fasting plasma insulin (PIns),triglycerides,total cholesterol,and low-density lipoprotein-cholesterol (LDL-C) were significantly higher,while the high-density lipoprotein-cholesterol(HDL-C)was lower in FGF-21-knockdown groups compared with control groups,respectively(P＜0.05 or P＜0.01).When fed with normal and high-fat diet,hepatic FGF-21 mRNA levels were decreased by 76.6％ (P＜0.05) and 40.9％ (P＜0.05) compared with those in control groups,while hepatic FGF-21protein levels were decreased by 67.8％ (P＜0.05) and 49.6％ (P＜0.05),respectively.The hepatic glucose-6-phosphatase(G6pase) and phosphoenolpyruvate carboxykinase (PEPCK)mRNA and protein expression in FGF-21-knockdown groups were significantly increased compared with those in control groups(P＜0.05).At the same time we observed decreased expression of hepatic SOCS3 mRNA and decreased expression of phosphorylated STAT3 and SOCS3 protein in FGF-21 knockdown groups.Conclusions FGF-21 can repress the expression of liver glyconeogenesis-related genes and its mechanism might involve the JAK2/STAT3 signaling pathway. Key words: Fibroblast growth factor-21; Gluconeogenesis; JAK2/STAT3 signaling pathway; Insulin resistance
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