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学科主题: 基础医学
题名:
Adipose-Specific Knockout of Seipin/Bscl2 Results in Progressive Lipodystrophy
作者: 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
发表日期: 2014-07-01
DOI: 10.2337/db13-0729
卷: 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
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
项目资助者: 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
WOS记录号: WOS:000337918200022
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/57166
Appears in Collections:基础医学院_心血管所_期刊论文

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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

Recommended Citation:
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.
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