PGRN is a Key Adipokine Mediating High Fat Diet-Induced Insulin Resistance and Obesity through IL-6 in Adipose Tissue

被引：269

作者：

Matsubara, Toshiya ^{[1
,2
,6
]}

Mita, Ayako ^{[2
,3
]}

Minami, Kohtaro ^{[2
]}

Hosooka, Tetsuya ^{[3
]}

Kitazawa, Sohei ^{[4
]}

Takahashi, Kenichi ^{[9
]}

Tamori, Yoshikazu ^{[3
,7
]}

Yokoi, Norihide ^{[2
]}

Watanabe, Makoto ^{[6
,8
]}

Matsuo, Ei-ichi ^{[6
,8
]}

Nishimura, Osamu ^{[1
,8
]}

Seino, Susumu ^{[1
,2
,3
,5
]}

机构：

[1] Kobe Univ, Grad Sch Med, Integrated Ctr Mass Spectrometry, Chuo Ku, Kobe, Hyogo 6500017, Japan

[2] Kobe Univ, Grad Sch Med, Div Cellular & Mol Med, Chuo Ku, Kobe, Hyogo 6500017, Japan

[3] Kobe Univ, Grad Sch Med, Div Diabet & Endocrinol, Chuo Ku, Kobe, Hyogo 6500017, Japan

[4] Kobe Univ, Grad Sch Med, Div Diagnost Mol Pathol, Chuo Ku, Kobe, Hyogo 6500017, Japan

[5] Japan Sci & Technol Agcy, Kawaguchi, Saitama 3320012, Japan

[6] Shimadzu Co Ltd, Life Sci Res Ctr, Technol Res Lab, Seika, Kyoto 6190237, Japan

[7] Chibune Hosp, Dept Internal Med, Ctr Diabet, Nishiyodogawa Ku, Osaka 5550001, Japan

[8] Osaka Univ, Div Dis Prote, Inst Prot Res, Suita, Osaka 5650871, Japan

[9] JCR Pharmaceut Co Ltd, Nishi Ku, Kobe, Hyogo 6512241, Japan

来源：

CELL METABOLISM | 2012年 / 15卷 / 01期

基金：

日本科学技术振兴机构;

关键词：

TUMOR-NECROSIS-FACTOR; 3T3-L1; ADIPOCYTES; FACTOR-ALPHA; GROWTH-FACTOR; CYTOKINE SIGNALING-3; BIOMARKER DISCOVERY; TNF-ALPHA; IN-VIVO; INTERLEUKIN-6; PROGRANULIN;

D O I：

10.1016/j.cmet.2011.12.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-alpha 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. Gm 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.

引用

页码：38 / 50

页数：13

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