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学科主题基础医学
Adipose-Specific Knockout of Seipin/Bscl2 Results in Progressive Lipodystrophy
Liu, Lu1,2; Jiang, Qingqing1,2; Wang, Xuhong3; Zhang, Yuxi4; Lin, Ruby C. Y.4; Lam, Sin Man5; Shui, Guanghou5; Zhou, Linkang6,7; Li, Peng6,7; Wang, Yuhui1,2; Cui, Xin1,2; Gao, Mingming1,2; Zhang, Ling1,2; Lv, Ying8; Xu, Guoheng8; Liu, George1,2; Zhao, Dong3; Yang, Hongyuan4
刊名DIABETES
2014-07-01
DOI10.2337/db13-0729
63期:7页:2320-2331
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Endocrinology & Metabolism
资助者Major National Basic Research Program of the People&prime ; s Republic of China ; National Natural Science Foundation of the People&prime ; s Republic of China ; National Health and Medical Research Council of Australia ; Major National Basic Research Program of the People&prime ; s Republic of China ; National Natural Science Foundation of the People&prime ; s Republic of China ; National Health and Medical Research Council of Australia
研究领域[WOS]Endocrinology & Metabolism
关键词[WOS]SEIP CONGENITAL LIPODYSTROPHY ; ACTIVATED RECEPTOR-GAMMA ; ADIPOCYTE DIFFERENTIATION ; LIPID DROPLETS ; PPAR-GAMMA ; FAT ; METABOLISM ; LIPOLYSIS ; PROTEIN ; TISSUE
英文摘要

Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) is the most severe form of human lipodystrophy, characterized by an almost complete loss of adipose tissue and severe insulin resistance. BSCL2 is caused by loss-of-function mutations in the BSCL2/SEIPIN gene, which is upregulated during adipogenesis and abundantly expressed in the adipose tissue. The physiological function of SEIPIN in mature adipocytes, however, remains to be elucidated. Here, we generated adipose-specific Seipin knockout (ASKO) mice, which exhibit adipocyte hypertrophy with enlarged lipid droplets, reduced lipolysis, adipose tissue inflammation, progressive loss of white and brown adipose tissue, insulin resistance, and hepatic steatosis. Lipidomic and microarray analyses revealed accumulation/imbalance of lipid species, including ceramides, in ASKO adipose tissue as well as increased endoplasmic reticulum stress. Interestingly, the ASKO mice almost completely phenocopy the fat-specific peroxisome proliferator-activated receptor-gamma (Ppar gamma) knockout (FKO-gamma) mice. Rosiglitazone treatment significantly improved a number of metabolic parameters of the ASKO mice, including insulin sensitivity. Our results therefore demonstrate a critical role of SEIPIN in maintaining lipid homeostasis and function of adipocytes and reveal an intimate relationship between SEIPIN and PPAR-gamma.

语种英语
所属项目编号2011CB503900 ; 2012CB517505 ; 30930037 ; 81121061 ; 30971102 ; 31228014 ; 1027387
资助者Major National Basic Research Program of the People&prime ; s Republic of China ; National Natural Science Foundation of the People&prime ; s Republic of China ; National Health and Medical Research Council of Australia ; Major National Basic Research Program of the People&prime ; s Republic of China ; National Natural Science Foundation of the People&prime ; s Republic of China ; National Health and Medical Research Council of Australia
WOS记录号WOS:000337918200022
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/57166
专题北京大学基础医学院_心血管所
作者单位1.Peking Univ, Inst Cardiovasc Sci, Hlth Sci Ctr, Minist Educ, Beijing 100871, Peoples R China
2.Peking Univ, Key Lab Mol Cardiovasc Sci, Hlth Sci Ctr, Minist Educ, Beijing 100871, Peoples R China
3.Capital Med Univ, Dept Endocrinol, Lu He Teaching Hosp, Beijing, Peoples R China
4.Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW, Australia
5.Chinese Acad Sci, State Key Lab Mol Dev Biol, Inst Genet & Dev Biol, Beijing, Peoples R China
6.Tsinghua Univ, MOE Key Lab Bioinformat, Sch Life Sci, Beijing 100084, Peoples R China
7.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Sch Life Sci, Beijing 100084, Peoples R China
8.Peking Univ, Dept Physiol & Pathophysiol, Hlth Sci Ctr, Sch Basic Med Sci, Beijing 100871, Peoples R China
推荐引用方式
GB/T 7714
Liu, Lu,Jiang, Qingqing,Wang, Xuhong,et al. Adipose-Specific Knockout of Seipin/Bscl2 Results in Progressive Lipodystrophy[J]. DIABETES,2014,63(7):2320-2331.
APA Liu, Lu.,Jiang, Qingqing.,Wang, Xuhong.,Zhang, Yuxi.,Lin, Ruby C. Y..,...&Yang, Hongyuan.(2014).Adipose-Specific Knockout of Seipin/Bscl2 Results in Progressive Lipodystrophy.DIABETES,63(7),2320-2331.
MLA Liu, Lu,et al."Adipose-Specific Knockout of Seipin/Bscl2 Results in Progressive Lipodystrophy".DIABETES 63.7(2014):2320-2331.
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