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中国应用生理学杂志 ›› 2018, Vol. 34 ›› Issue (1): 88-92.doi: 10.12047/j.cjap.5507.2018.022

• 研究论文 • 上一篇    下一篇

低氧对肥胖小鼠棕色脂肪组织相关基因表达的影响及其机制

龚丽景1, 付鹏宇2, 朱鑫2, 汪蕾1, 胡扬1   

  1. 1. 北京体育大学中国运动与健康研究院, 北京 100084;
    2. 北京体育大学运动人体科学学院, 北京 100084
  • 收稿日期:2016-10-10 修回日期:2017-06-23 出版日期:2018-01-28 发布日期:2018-06-19
  • 通讯作者: 胡扬,Tel:010-62989208;E-mail:hyyr1@163.com E-mail:hyyr1@163.com
  • 基金资助:
    国家自然科学基金(31470059);中央高校基本科研业务费专项资金(2015SYS010)

Effects and mechanism of hypoxia exposure on related genes in brown fat tissue of obese mice based on mRNA expression profile microarray

GONG Li-jing1, FU Peng-yu2, ZHU Rong-xin2, WANG Lei1, HU Yang1   

  1. 1. Chinese Academy of Sports and Health, Beijing Sport University, Beijing 100084, China;
    2. Sport Science College, Beijing Sport University, Beijing 100084, China
  • Received:2016-10-10 Revised:2017-06-23 Online:2018-01-28 Published:2018-06-19
  • Supported by:
    国家自然科学基金(31470059);中央高校基本科研业务费专项资金(2015SYS010)

摘要: 目的:分析肥胖小鼠在低氧暴露后棕色脂肪组织的差异表达基因及通路,以探讨低氧影响棕色脂肪组织活化的机制。方法:30只雄性C57BL/6J小鼠,其中8只为普通对照组(N,n=8);其余饲喂高脂饲料8周后,肥胖建模成功小鼠随机分为两组:肥胖对照组(OB,n=8)和肥胖低氧组(H,n=8)。H组进行11.2%氧浓度8 h/d,6天/周共4周的低氧暴露。4周后,测试血糖、血脂,取肩胛处棕色脂肪组织进行mRNA表达谱芯片扫描和生物信息学分析。利用KOBAS2.0软件对所筛选差异表达基因,并对参与关键生物过程和信号通路的差异基因进行实时荧光qPCR验证。结果:干预结束后,H组较OB组体重和血脂血糖水平显著降低;OB组较N组的上调差异基因802个,下调1 175个,差异基因的功能主要集中在糖脂合成代谢及免疫炎症反应过程;H组较OB组上调基因297个,下调228个,主要参与的生物过程有糖脂代谢、脂质转运过程、肌肉组织发育过程及脉管系统发育过程;低氧暴露调节肥胖机体棕色脂肪的通路主要集中在HIF-1、PI3K-Akt、FoxO和ErbB信号通路等过程。结论:11.2%氧气暴露可通过调节一系列棕色脂肪相关基因表达而提高棕色脂肪活性,从而下调肥胖机体体重。

关键词: mRNA表达谱, 棕色脂肪, 低氧暴露, 肥胖, 小鼠

Abstract: Objective: This study intended to screen differentially expressed genes and pathways in Brown Adipose Tissue (BAT) of obese mice after the intervention of hypoxia by mRNA expression profile microarray, exploring the mechanism of hypoxia activated BAT.Methods: Thirty C57BL/6J male mice were divided into the normal diet control group (N, n=8), high-fat diet control group (OB, n=8) and high-fat diet hypoxia group (H, n=8). Group H was intervened by hypoxia exposure in the oxygen concentration of 11.2% of the normal oxygen and hypoxia for 8 h/d, 6 d/w of 4 weeks. Blood lipid and blood glucose were detected after intervention; RNA microarray scan and bioinformation analysis were done of BAT from scapula. Genes significantly (P ≤ 0.05) regulated more than 1.5 fold were chosen to do Gene Ontology and enrichment analysis by KOBAS 2.0, and confirmation of genes participating in key biological process (BP) and pathway was done by real time qPCR.Results: After intervention, the body weight and blood lipid and glucose levels in group H were significantly lower than those of group OB. Comparing with group N, 802 genes were significantly up-regulated and 1 175genes were down-regulated. The BP of these genes mainly concerned with glucose and lipid metabolic process and inflammatory reaction. Comparing with group OB, 297 genes were significantly up-regulated and 228 genes were down-regulated. These genes participated in glucose and lipid metabolic process, lipid transport, muscle system process and cardiovascular system development. The pathways of regulating BAT by hypoxia exposure mainly concentrated on the HIF-1, PI3K-AKT, FoxO and ErbB signaling pathways.Conclusion: A series of genes and pathways in BAT could be adjusted by hypoxia exposure, so that hypoxia could improve the activity of BAT, promoting obese organism to lose weight.

Key words: gene expression profiling, brown adipose tissue, hypoxia, obesity, mice

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