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首页 > 过刊浏览>2018年第28卷第4期 >1-6. DOI:10.3969/j. issn. 1671 -7856. 2018. 04. 001
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FKBP 51 参与高脂诱导的线粒体损伤
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作者单位:

(中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,卫生部人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室,北京 100021)

中图分类号:

R-33

基金项目:

中国医学科学院医学创新基金(DCIFM 2017-I2M-3-015);国家自然科学基金(81700751,81272273);北京市自然科学基金(7164278)


Involvement of FKBP 51 in mitochondrial damage induced by high fat diet feeding
Author:
  • LIU Ming

    LIU Ming

    Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China
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  • QIU Bin

    QIU Bin

    Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China
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  • WANG Tingting

    WANG Tingting

    Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China
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  • DENG Ran

    DENG Ran

    Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China
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  • LIU Yunbo

    LIU Yunbo

    Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China
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  • YONG Weidong

    YONG Weidong

    Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China
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Affiliation:

(Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) & Comparative Medicine Center, Peking Union Medical College (PUMC); Key Laboratory of Human Disease Comparative Medicine, Ministry of Health; Key Laboratory of Human Disease Animal Models, State Administration of Traditional Chinese Medicine, Beijing 100021, China)

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    摘要:

    目的 通过高脂喂养C57BL/6J 小鼠,探究小鼠高脂饮食对线粒体结构和功能的影响?方法 随机选取4 周龄雄性C57BL/6J 小鼠,分别进行正常饮食和高脂饮食饲养6 周后通过体重和HE 染色确认高脂诱导的肥胖表型,利用二代测序技术对正常饮食和高脂饮食小鼠肝脏mRNA 表达谱测序并用BRB-ArrayTools 筛选差异基因,对差异基因进行GO 本体分析和KEGG 通路分析,应用透射电镜和western blotting 技术检测高脂饮食下小鼠肝脏线粒体显微结构及相关功能蛋白的表达情况?结果 与正常饮食组小鼠相比,高脂饮食组小鼠体重显著增加,肝脏中脂肪沉积明显增多?利用DAVID 在线工具对差异基因进行GO 本体分析及KEEG 通路分析,发现这些主要基因变化与线粒体相关?通过透射电镜观察,发现高脂饮食组小鼠线粒体变形?增大甚至破裂坏死?此外,高脂饮食组小鼠肝脏线粒体中线粒体融合蛋白(mitofusin 1,MFN1)和抗增殖蛋白1(prohibitin1,PHB1)的相对表达量显著增加,而 FKBP P51 的表达量显著降低?结论 FKBP51 通过影响线粒体形态与结构来参与高脂诱导的线粒体损伤?

    Abstract:

    Objective To investigate the effect of high fat diet feeding on mitochondrial structure and function. Methods Male C57BL/6J mice at the age of 4 weeks were used in this study. After 6 weeks of regular diet (RD) or high-fat diet (HF) feeding, the high fat-induced obesity phenotype was confirmed by body weight measurement and liver histopathology. RNA was isolated from the liver tissue of RD and HF mice and the expression profiles were detected using RNA-seq. Differentially expressed genes between RD and HF mice were analyzed using BRB-ArrayTools. DAVID online tools were applied to analyze the GO and KEGG pathways. Transmission electron microscopy and western blotting were performed to observe the mitochondrial ultrastructure and quantified the expression of function-related proteins. Results Compared with the RD mice, the body weight gain was faster in the HF mice. The size of the lipid droplets was bigger in the HF-fed mouse liver tissue. Multiple pathway analysis all identified that these major gene changes were related to mitochondria. The mitochondrial deformation, enlarged or even destruction was observed in the high fat diet group observed by transmission electron microscopy. This observation was further confirmed by detecting of the expression of genes in the HF liver mitochondria. The levels of MFN1 and PHB1 were significantly increased, while the level of FKBP51 was significantly decreased. Conclusions FKBP 51 is involved in the high-fat-induced mitochondrial damage via morphological and structural damages of mitochondria.

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刘明,邱彬,王婷婷,邓然,刘云波,雍伟东. FKBP 51 参与高脂诱导的线粒体损伤[J].中国比较医学杂志,2018,28(4):1~6.

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历史
  • 收稿日期:2017-09-20
  • 在线发布日期: 2018-05-22
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