富生酮氨基酸饮食对高脂诱导的小鼠胰岛素抵抗的影响  

Effects of ketogenic amino acid replacement diet on insulin resistance in mice fed with high fat diet

作　　者：徐玲[1] 马红艳[1] 李佳[1] 高陈林[1] 徐勇[1] 

机构地区：[1]泸州医学院附属医院内分泌科,646000

出　　处：《中华内分泌代谢杂志》2016年第5期399-404,共6页Chinese Journal of Endocrinology and Metabolism

基　　金：四川省卫生厅科研基金资助项目（120330）

摘　　要：目的：探讨富生酮氨基酸饮食对高脂诱导小鼠胰岛素抵抗的影响及机制。方法 C57BL小鼠随机分4组,给予常规饮食（ Con）、高脂饮食（ HFD）、富生酮氨基酸高脂饮食（ HFDKAAR ）以及高脂喂养8周后改为富生酮氨基酸高脂饮食（ HFD→HFDKAAR ）喂养。测食量、体重及内脏脂肪,16周后行腹腔内葡萄糖耐量试验,测血糖、胰岛素、血酮,根据血糖和胰岛素计算曲线下面积（ AUC）及胰岛素抵抗指数（ IRI）,检测肝脏LKB1、AMPK、mTOR蛋白和mcp-1 mRNA表达。结果各组小鼠摄入量及血酮无统计学差异。与Con组比较,HFD组小鼠表现体重及内脏脂肪增加、糖耐量受损和高胰岛素水平,肝LKB1、p-AMPK表达下降,p-mTOR蛋白和mcp-1 mRNA表达增加。与HFD比较,HFDKAAR及HFD→HFDKAAR组小鼠体重及内脏脂肪均减轻,血糖、AUC、胰岛素浓度和IRI均降低（P〈0.05）,肝LKB1、p-AMPK、p-mTOR蛋白和mcp-1 mRNA表达异常均被明显逆转（P〈0.05）。结论富生酮氨基酸饮食可能通过调节肝脏LKB1-AMPK-mTOR通路,降低mcp-1 mRNA水平,改善或逆转高脂饮食诱导的肥胖、胰岛素抵抗及糖耐量受损。Objective To investigate the effects of ketogenic amino acid （ KAA） replacement diet on insulin resistance in mice fed with high fat diet（HFD） and to analyze the possible mechanism. Methods C57BL mice were fed with a control diet, HFD, and KAA-fortified HFD（HFDKAAR）from the age of 8 weeks, and 8 weeks after HFD initiation, the HFD-fed mice were divided into two groups：one group of mice were fed the same HFD, the other group were fed HFDKAAR （ HFD→HFDKAAR ） . The metabolic evaluations were performed at the end of 16 weeks. Blood glucose levels were measured at 0, 15, 30, 60, 90, and 120 min after the injection of glucose （ 1 g/kg BW intraperitoneal glucose tolerance test, ipGTT） . The insulin,β-hydroxybutyrate, and acetoacetate levels in the plasma were measured via ELISA. The insulin resistance index （ IRI） and area under curve （ AUC） were calculated. The expression of hepatic LKB1 （ liver kinase B1 ） , AMP-activated protein kinase （ AMPK ） , and mTOR （ Mammalian target of rapamycin ） protein, and mcp-1 mRNA were measured by western blot and real-time PCR respectively. Results HFD-fed group of mice displayed significantly heavier body weight,heavier intra-abdominal fat weight, and significant deterioration of glucose tolerance at the end of 16 weeks in addition to higher insulin levels（ all P〈0. 05）, HFDKAAR-fed mice exhibited significantly ameliorated high fat diet-induced obesity and glucose intolerance compared to the HFD-fed mice, which was associated with decreased insulin levels, IRI, AUC, and mcp-1 mRNA expression （all P〈0. 05）. HFD suppressed hepatic LKB1 and AMPK phosphorylation expression, and increased mTOR phosphorylation levels compared to the control diet-fed mice（all P〈0. 05）. In contrast, treatment with the HFDKAAR diet increased LKB1and p-AMPK expression, which was associated with suppressed p-mTOR levels compared to the HFD-fed mice（all P〈0. 05）. Conclusion KAA may ameliorate high fat diet-induced obesity, glucose intolerance,

关 键 词：氨基酸 胰岛素抵抗 代谢综合征 

分 类 号：R58[医药卫生—内分泌]