Document Detail


PGRN is a Key Adipokine Mediating High Fat Diet-Induced Insulin Resistance and Obesity through IL-6 in Adipose Tissue.
MedLine Citation:
PMID:  22225875     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Adipose tissue secretes adipokines that mediate insulin resistance, a characteristic feature of obesity and type 2 diabetes. By differential proteome analysis of cellular models of insulin resistance, we identified progranulin (PGRN) as an adipokine induced by TNF-α and dexamethasone. PGRN in blood and adipose tissues was markedly increased in obese mouse models and was normalized with treatment of pioglitazone, an insulin-sensitizing agent. Ablation of PGRN (Grn(-/-)) prevented mice from high fat diet (HFD)-induced insulin resistance, adipocyte hypertrophy, and obesity. Grn deficiency blocked elevation of IL-6, an inflammatory cytokine, induced by HFD in blood and adipose tissues. Insulin resistance induced by chronic administration of PGRN was suppressed by neutralizing IL-6 in vivo. Thus, PGRN is a key adipokine that mediates HFD-induced insulin resistance and obesity through production of IL-6 in adipose tissue, and may be a promising therapeutic target for obesity.
Authors:
Toshiya Matsubara; Ayako Mita; Kohtaro Minami; Tetsuya Hosooka; Sohei Kitazawa; Kenichi Takahashi; Yoshikazu Tamori; Norihide Yokoi; Makoto Watanabe; Ei-Ichi Matsuo; Osamu Nishimura; Susumu Seino
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell metabolism     Volume:  15     ISSN:  1932-7420     ISO Abbreviation:  Cell Metab.     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-01-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101233170     Medline TA:  Cell Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  38-50     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
Affiliation:
Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan; The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan; Life Science Research Center, Technology Research Laboratory, Shimadzu Corporation, 3-9-4 Hikaridai, Seika-cho, Soraku-gun, Kyoto 619-0237, Japan.
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