FGF21对MSG胰岛素抵抗小鼠的非酒精性脂肪肝的治疗作用及其机制研究

Therapeutic effect of fibroblast growth factor 21 on NAFLD in MSG-IR mice and its mechanism

研究成纤维细胞生长因子21(fibroblast growth factor 21,FGF21)对谷氨酸钠(MSG)肥胖小鼠非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)的治疗作用及其作用机制。实验分为正常对照组、模型对照组、高剂量FGF21治疗组和低剂量FGF21治疗组。给药5周,给药期间每周监测小鼠体重,给药结束时测定血脂和血清胰岛素及转氨酶含量。Real-time PCR方法检测肝脏和脂肪组织内能量代谢调节关键基因表达。结果显示,治疗5周后,不同剂量FGF21均明显降低MSG模型体重(P<0.01),纠正其血脂紊乱(P<0.01),减轻模型小鼠的肝内脂肪变性,恢复其肝脏细胞正常形态结构,并且可显著改善MSG模型鼠胰岛素抵抗状态。因此,FGF21能显著减轻MSG肥胖小鼠体重、改善胰岛素抵抗、逆转模型小鼠的肝内脂肪变性,这一发现为临床应用FGF21治疗非酒精性脂肪肝奠定了理论基础。

This study is to evaluate the therapeutic effect of fibroblast growth factor 21 （FGF21） on NAFLD in MSG-IR mice and to provide mechanism insights into its therapeutic effect. The MSG-IR mice with insulin resistance were treated with high dose （0.1 mol.kg-l.d-l） and low dose （0.025mol.kg-l.d-1） of FGF21 once a day for 5 weeks. Body weight was measured weekly. At the end of the experiment, serum lipids, insulin and aminotransferases were measured. Hepatic steatosis was observed. The expression of key genes regulating energy metabolism were detected by real-time PCR. The results showed that after 5 weeks treatment, both doses of FGF21 reduced body weight （P〈0.01）, corrected dyslipidemia （P〈0.01）, reversed steatosis and restored the liver morphology in the MSG model mice and significantly ameliorated insulin resistance. Additionally, real-time PCR showed that FGF21 significantly reduced transcription levels of fat synthetic genes, decreased fat synthesis and promoted lipolysis and energy metabolism by up-regulating key genes of lipolysis, thereby liver fat accumulation was reduced and liver function was restored to normal levels. In conclusion, FGF21 significantly reduces bodyweight of the MSG-IR mice, ameliorates insulin resistance, reverses hepatic steatosis. These findings provide a theoretical support for clinical application of FGF21 as a novel therapeutics for treatment of NAFLD.