AKT/FOXO1信号通路在限热卡高脂饮食改善肥胖小鼠肝脏胰岛素抵抗中的作用  

The effect of AKT/FOXO1 signaling pathway on ameliorating obese mice hepatic insulin resistance with calorie restricted and high fat diet

作　　者：王鑫蕾[1] 倪晓晴[2] 苏建友[3] 袁瑾[1] 赵小芹[1] 周冉冉[1] 崔世维[1] 蒋燕秋 顾云娟[1] WANG Xinlei;NI Xiaoqing;SU Jianyou;YUAN Jin;ZHAO Xiaoqin;ZHOU Ranran;CUI Shiwei;JIANG Yanqiu;GU Yunjuan(Department of Endocrinology and Metabolism of Affiliated Hospital of Nantong University,Nantong 226001,China;不详)

机构地区：[1]南通大学附属医院内分泌科,南通226001 [2]南通大学附属医院老年医学科,南通226001 [3]南通大学附属医院检验科,南通226001

出　　处：《实用医学杂志》2020年第16期2199-2204,共6页The Journal of Practical Medicine

基　　金：南通市科技计划项目(编号:JC2018015,HS2014036,MS22019005);江苏省六大人才高峰项目(编号:2016-WSN-098);江苏省卫生计生委预防医学会基金(编号:Y2015070)。

摘　　要：目的研究AKT/FOXO1信号通路介导限热卡高脂饮食干预后的肥胖小鼠肝脏胰岛素抵抗中的作用。方法4周龄雄性C57BL/6J小鼠随机分为高脂喂养组(HFD组)及对照组(CON组),12周后,将HFD组小鼠随机分为继续高脂组(CHFD)、低热卡高脂组(LCHFD)和极低热卡高脂组(VLCHFD),继续喂养12周。观察喂养24周后各组小鼠总胆固醇(TC)、甘油三酯(TG)等生化指标,磷酸烯醇丙酮酸羧激酶(PEPCK)和葡萄糖-6-磷酸酯酶(G6Pase)及叉头框蛋白O1(FOXO1)的基因表达,磷酸化与非磷酸化AKT、FOXO1的蛋白定量。结果喂养24周后,CHFD组小鼠肝组织FOXO1、PEPCK和G6Pase的mRNA表达水平显著高于CON组,而随着饮食热卡的减少,CHFD组、LCHFD组及VLCHFD组FOXO1、PEPCK和G6Pase基因表达逐渐下降。同时,CHFD组小鼠p-AKT/AKT、p-FOXO1/FOXO1蛋白定量比值显著低于CON组,随着饮食热卡的减少,CHFD组、LCHFD组及VLCHFD组则逐渐增高。结论限热卡高脂饮食不仅能有效的控制肥胖小鼠的体质量、血糖及血脂,也能有效地逆转肥胖小鼠的非酒精性脂肪肝,而AKT/FOXO1信号通路在这一过程中起到了重要作用。Objective To investigate the effect of AKT/FoxO1 signaling pathway on ameliorate hepatic insulin resistance of obese mice fed with calorie restricted and high fat diet.Methods Fourweeks old male C57 BL/6 J mice were randomly divided into high fat diet group(HFD)and control group(CON).After 12 weeks,HFD mice were randomly divided into continual high fat diet group(CHFD),low calorie high fat diet group(LCHFD)and very low calorie high fat diet group(VLCHFD).At 24-week,weight,FPG,lipids,ALT,FINS,HOMA-IR of mice were compared among the four groups.The livers of mice were collected for HE statin.The mRNA levels of hepatic FOXO1,EPCK,G6 Pase and protein levels of p-FOXO1/FOXO1 and p-AKT/AKT were detected by RTqPCR and western blot separately.Results At 24-week,the weight,FPG,lipids,ALT,FINS,HOMA-IR were higher in CHFD group compared with CON group(P<0.05 for all),but above indices decreased gradually in CHFD,LCHFD and VLCHFD groups following the reduction of diet calorie.Otherwise,the vacuolar degeneration of hepatocytes were most seriously in CHFD group,and the mRNA levels of FOXO1,PEPCKand G6 Pase were also higher in CHFD group compared with CON group(P<0.05 for all),along with the reduction of diet calorie,the vacuolar degeneration of hepatocytes ameliorated and the mRNA levels of FOXO1,PEPCKand G6 Pase increased gradually.The protein ratios of p-FOXO1/FOXO1 and p-AKT/AKT were the lowest in CHFD group(P<0.05),but increased in CHFD,LCHFD and VLCHFD groups following the reduction of diet calorie.Conclusion Calorie restricted and high fat diet can significantly reduce body weight,ameliorate the metabolic dysfunction,reverse the vacuolar degeneration of hepatocytes in obese mice,and the FOXO1/AKT signaling pathway plays the important role.

关 键 词：AKT/FOXO1信号通路 肝脏胰岛素抵抗 高脂饮食 低热卡饮食 肥胖 

分 类 号：R589[医药卫生—内分泌]