短期高脂喂养诱导脂肪肝的肝胰岛素敏感性和炎性因子变化

The change of hepatic insulin sensitivity and inflammation factors in fatty liver induced by short-term high fat feeding

目的探讨短期(3日)高脂饮食对小鼠肝脏三酰甘油(TG)含量、肝胰岛素敏感性及肝脏炎性通路的影响。方法雄性C57BL/J6小鼠分为对照组及高脂组,经喂养3 d后处死小鼠,测定空腹血糖、血TG及血清谷丙转氨酶(AST),应用GPO-PAP法测定各组肝脏TG含量,应用Western blot法测定磷酸化Akt/总Akt、磷酸化GSK-3α/β/总GSK-3α/β以及JNK途径(磷酸化-JNK/总JNK)和IKKα/β-NF-κB(磷酸化-IKKα/β/总IKKα/β,NF-κB)途径的蛋白表达。结果喂养3日后,高脂组小鼠的空腹血糖、血TG、血AST较对照组无明显变化;高脂组的肝TG含量较对照组显著增加,分别为11.03±0.29和24.92±2.98(mmol/g)(P<0.01);高脂组小鼠胰岛素刺激后磷酸化Akt/总Akt和磷酸化GSK-3α/β/总GSK-3α/β比值较对照组减少(P<0.01);高脂组的磷酸化-JNK/总JNK的蛋白表达较对照组显著增加(P<0.01)。结论肝脏JNK炎性通路介导了高脂喂养诱导早期脂肪肝和胰岛素抵抗的发生发展。

Objective To investigate the effect of short-term（3 days） high fat feeding on liver triglyceride content,hepatic insulin sensitivity and hepatic inflammation pathways.Methods Male C57BL/J6 mice（~30 g） were fed a standard chow（Con） or high fat diet（HF）.Mice were sacrificed after 3-day feeding.Fasting blood glucose,serum triglyceride and serum alanine transaminase（ALT） were measured.Triglyceride content in liver was measured with GPO method.Western blot method were applied to detect the protein contents of phosphorylated-Akt/total-Akt,phosphorylated-GSK-3α/β/total-GSK-3α/β,phosphorylated-JNK/ total-JNK in JNK pathway,phosphorylated-IKKα/β/total-IKKα/β and NF-κB in IKKα/β-NF-κB pathway.Results After 3-day feeding,fasting blood glucose,serum TG and serum AST were unaltered in high fat group as compared with control group.Liver triglyceride content was significantly increased in high fat group than in control group（P0.01）,which were 11.03±0.29 and 24.92±2.98（mmol/g） respectively（P0.01）.The ratio of phosphorylated-Akt/total-Akt and phosphorylated-GSK-3α/β/ total-GSK-3α/βwere significantly decreased in HF group than in control group after insulin stimulation（P0.01）.The protein expression of p-JNK/t-JNK was significantly increased in high-fat group than in control group（P0.01）.Conclusions JNK pathway in liver is involved in the early development of fatty liver and hepatic insulin resistance induced by high-fat-feeding.