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|本期目录/Table of Contents|

支链氨基酸促进高脂诱导的小鼠肝脏胰岛素抵抗

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2016年第6期
页码:
629-633
栏目:
基础研究
出版日期:
2016-07-05

文章信息/Info

Title:
Branched chain amino acids facilitate high-fat-induced insulin resistance in mice liver
作者:
赵会寿1; 廉 坤1; 闫 凤1; 郭 雄1; 黄 冲1; 刘朝中2; 陶 凌1
（1.第四军医大学西京医院心血管内科，陕西 西安 710032；2.空军总医院心内科，北京 100036）
Author(s):
ZHAO Hui-shou1;  LIAN Kun1;  YAN Feng1;  GUO Xiong1;  HUANG Chong1;  LIU Chao-zhong2;  TAO Ling1
(1.Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China；
2.Department of Cardiology, Air Force General Hospital, Beijing 100036, China)
关键词:
支链氨基酸; 2型糖尿病; 胰岛素抵抗
Keywords:
branched chain amino acids;  type 2 diabetes;  insulin resistance
分类号:
R587.1
DOI:
-
文献标识码:
A
摘要:
目的 探讨支链氨基酸（Branched chain amino acids,BCAA）对高脂诱导胰岛素抵抗的影响。方法 将60只野生C57BL/6J小鼠随机分成4组，分别给予正常饮食+普通饮水（ND）组，正常饮食+含50 g/L BCAA饮水（ND/BCAA）组，高脂饮食（HD）组，高脂饮食+含50 g/L BCAA饮水（HD/BCAA）组，喂养18周，仔细观察小鼠生活状态并每周记录小鼠体质量，18周后进行葡萄糖耐量（IPGTT）和胰岛素耐量（ITT）实验，检测小鼠血清BCAA和胰岛素水平，Western blot检测小鼠肝脏胰岛素信号通路关键分子IRS1及其磷酸化水平〔p-IRS1(ser307)〕、AKT及其磷酸化水平〔p-AKT(ser473)〕。结果 ①BCAA抑制高脂诱导的小鼠体质量增加，表现为HD/BCAA组小鼠体质量增长比HD组缓慢（P<0.05，P<0.01）；ND/BCAA组和ND组体质量增长无明显差异；②与ND组相比，ND/BCAA组小鼠血清BCAA浓度无明显升高，HD组血清BCAA水平升高（P<0.05）；与HD组相比，HD/BCAA组血清BCAA浓度进一步升高（P<0.05）；③与ND组相比，ND/BCAA组小鼠血清胰岛素、IPGTT和ITT均无明显改变；与HD组相比，HD/BCAA组血清胰岛素水平更高，IPGTT和ITT均明显受损（P<0.05）；④Western blot检测显示：ND组和ND/BCAA组小鼠肝脏p-IRS1(ser307)和p-AKT(ser473)水平无明显改变；与ND组相比，HD组小鼠p-IRS1(ser307)上调（P<0.05），IRS1、p-AKT(ser473)均下调（P<0.05，P<0.01）；与HD组相比，HD/BCAA组小鼠肝脏p-IRS1(ser307)进一步上调（P<0.05），p-AKT(ser473)水平进一步下调（P<0.01）。结论 正常饮食单纯补充BCAA不影响小鼠肝脏胰岛素敏感性， BCAA能够促进高脂诱导的小鼠肝脏胰岛素抵抗。
Abstract:
AIM To investigate the effect of branched chain amino acids (BCAA) on high-fat-induced insulin resistance. METHODSSixty wild-type C57BL/6J mice were randomly divided into four groups and were offered a choice of normal diets with tap water (ND group), normal diets with tap water containing 50 g/L BCAA (ND/BCAA group), high-fat diets (HD group), and high-fat diets with tap water containing 50 g/L BCAA (HD/BCAA group) for 18 weeks. Status of mice in each group was carefully observed and body weight was recorded every week. We then performed glucose and insulin tolerance tests, detected the serum level of BCAA and insulin in mice, and detected liver insulin signaling key molecules IRS1 and its phosphorylation level ［p-IRS1(ser307)］, AKT and its phosphorylation level ［p-AKT(ser473)］ by Western blot. RESULTSBCAA supplementation inhibited body weight gain induced by high-fat diets, and body weight gain in the HD/BCAA group was significantly lower compared with HD group (P<0.05, P<0.01). Body weight gain between ND group and ND/BCAA group was not significantly different. Compared with the ND group, serum BCAA concentration in the ND/BCAA group was not significantly increased, whereas the serum level of BCAA in HD group was significantly higher (P<0.05) and the BCAA level in HD/BCAA group increased further (P<0.05) compared with HD group. Compared with ND group, serum insulin level, glucose and insulin tolerances in ND/BCAA group were not significantly different. HD/BCAA group showed a higher serum insulin level, impaired glucose and insulin tolerance compared with HD group (P<0.05). Western blot showed that p-IRS1 (ser307) and p-AKT (ser473) levels were not significantly different between ND group and ND/BCAA group. When compared with ND group, HD group showed up-regulated p-IRS1 (ser307) (P<0.05) and down-regulated IRS1 and p-AKT (ser473) (P<0.05, P<0.01). HD/BCAA group showed a further up-regulated p-IRS1 (ser307) (P<0.05) and more down-regulated p-AKT (ser473) (P<0.01) when compared with HD group. CONCLUSIONNormal diets supplemented with BCAA did not affect liver insulin sensitivity in mice, but BCAA facilitates high-fat-induced insulin resistance in the liver.

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备注/Memo

备注/Memo:
收稿日期：2015-12-02.
基金项目：国家杰出青年科学基金项目资助（81225002）；国家重点基础研究发展计划项目资助（2013CB531204）；国家自然科学基金青年科学基金项目资助（81500272）
通讯作者：陶凌，主任医师，主要从事糖尿病心肌损伤研究Email: lingtao@fmmu.edu.cn
共同通讯作者：刘朝中，主任医师，主要从事冠心病的诊治和基础研究Email:liu_chaozhong@sohu.com
作者简介：赵会寿，硕士生Email:1054395879@qq.com
更新日期/Last Update: 2016-07-10