Effects Of FGF-21Gene Knockdown On Hepatic Gluconeogenesis-related Genes Expression In ApoE^-/- Mice And Its Mechanism

Objective: To clarify the effects of FGF-21gene knockdown onglyconeogenesis-related genes expression in ApoE-/-mice and itsmechanism.Method:248-week-old male ApoE-/-mice were accidentallydistributed into chow-diet-fed control group(NC, n=6), chow-diet+pAd-shFGF-21group（NF，n=6）,high-fat-diet-fed control group(HC，n=6)and high-fat-diet+pAd-shFGF-21group（HF，n=6）.Mice were kept for16weeks.NF and HF groups were injected with pAd-shFGF-21through thetail vein at the end of the15th week.At the end of the16th week, execute themice and collect their livers to measure the expression ofglyconeogenesis-related genes and JAK2/STAT3signaling pathway viareal-time quantitive PCR and Western-blot.Results: When fed with normal and high-fat-diet, hepatic FGF-21mRNA levels were decreased by76.6%（p <0.05）and40.9%（p <0.05） compared with those in control groups, while hepaticFGF-21protein levels were decreased by67.8%（p<0.05）and 49.6%（p <0.05）. The hepatic G6pase and PEPCK mRNA and proteinexpression in FGF-21-konckdown groups were significantly increasedcompared with those in control groups（p<0.05）.At the same time weobserved decreased expression of hepatic SOCS3、 IL-6mRNA anddecreased expression of phosphorylated STAT3and SOCS3protein inFGF-21-konckdown groups。Conclusion: FGF-21can restrain the expression of liverglyconeogenesis-related genes and its mechanism might relate toJAK2/STAT3signaling pathway.