Hepatic protein tyrosine phosphatase receptor gamma links obesity-induced inflammation to insulin resistance

被引：56

作者：

Brenachot, Xavier ^{[1
,2
]}

Ramadori, Giorgio ^{[1
,2
]}

Ioris, Rafael M. ^{[1
,2
]}

Veyrat-Durebex, Christelle ^{[1
,2
]}

Altirriba, Jordi ^{[2
,3
]}

Aras, Ebru ^{[1
,2
]}

Ljubicic, Sanda ^{[1
,2
]}

Kohno, Daisuke ^{[4
,5
]}

Fabbiano, Salvatore ^{[1
,2
]}

Clement, Sophie ^{[6
]}

Goossens, Nicolas ^{[7
]}

Trajkovski, Mirko ^{[1
,2
]}

Harroch, Sheila ^{[8
,9
]}

Negro, Francesco ^{[2
,6
,7
]}

Coppari, Roberto ^{[1
,2
]}

机构：

[1] Univ Geneva, Fac Med, Dept Cell Physiol & Metab, CH-1211 Geneva 4, Switzerland

[2] Univ Geneva, Fac Med, Diabet Ctr, CH-1211 Geneva 4, Switzerland

[3] Univ Geneva, Fac Med, Dept Internal Med Specialties, Lab Metab, CH-1211 Geneva, Switzerland

[4] Gunma Univ, Adv Sci Res Leaders Dev Unit, 3-39-15 Showa Machi, Maebashi, Gunma 3718512, Japan

[5] Gunma Univ, Inst Mol & Cellular Regulat, Metab Signal Res Ctr, 3-39-15 Showa Machi, Maebashi, Gunma 3718512, Japan

[6] Geneva Univ Hosp, Clin Pathol, Rue Gabrielle Perret Gentil, CH-1211 Geneva 14, Switzerland

[7] Geneva Univ Hosp, Gastroenterol & Hepatol, Rue Gabrielle Perret Gentil, CH-1211 Geneva 14, Switzerland

[8] NYU, Dept Psychiat, Langone Sch Med, 550 1st Ave, New York, NY 10016 USA

[9] Inst Pasteur, Dept Neurosci, F-75824 Paris, France

来源：

NATURE COMMUNICATIONS | 2017年 / 8卷

基金：

瑞士国家科学基金会; 欧洲研究理事会;

关键词：

DIET-INDUCED OBESITY; NF-KAPPA-B; SIRT1; DEACETYLASE; MITOCHONDRIAL-FUNCTION; DIABETES-MELLITUS; STRUCTURAL BASIS; TNF-ALPHA; IKK-BETA; ACTIVATION; INHIBITION;

D O I：

10.1038/s41467-017-02074-2

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Obesity-induced inflammation engenders insulin resistance and type 2 diabetes mellitus (T2DM) but the inflammatory effectors linking obesity to insulin resistance are incompletely understood. Here, we show that hepatic expression of Protein Tyrosine Phosphatase Receptor Gamma (PTPR-gamma) is stimulated by inflammation in obese/T2DM mice and positively correlates with indices of inflammation and insulin resistance in humans. NF-kappa B binds to the promoter of Ptprg and is required for inflammation-induced PTPR-gamma expression. PTPR-gamma loss-of-function lowers glycemia and insulinemia by enhancing insulin-stimulated suppression of endogenous glucose production. These phenotypes are rescued by re-expression of Ptprg only in liver of mice lacking Ptprg globally. Hepatic PTPR-gamma overexpression that mimics levels found in obesity is sufficient to cause severe hepatic and systemic insulin resistance. We propose hepatic PTPR-gamma as a link between obesity-induced inflammation and insulin resistance and as potential target for treatment of T2DM.

引用

页数：9

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