Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation.

Abstract:

:Chronic low-grade inflammation is emerging as a pathogenic link between obesity and metabolic disease. Persistent immune activation in white adipose tissue (WAT) impairs insulin sensitivity and systemic metabolism, in part, through the actions of proinflammatory cytokines. Whether obesity engages an adaptive mechanism to counteract chronic inflammation in adipose tissues has not been elucidated. Here we identified otopetrin 1 (Otop1) as a component of a counterinflammatory pathway that is induced in WAT during obesity. Otop1 expression is markedly increased in obese mouse WAT and is stimulated by tumor necrosis factor-α in cultured adipocytes. Otop1 mutant mice respond to high-fat diet with pronounced insulin resistance and hepatic steatosis, accompanied by augmented adipose tissue inflammation. Otop1 attenuates interferon-γ (IFN-γ) signaling in adipocytes through selective downregulation of the transcription factor STAT1. Using a tagged vector, we found that Otop1 physically interacts with endogenous STAT1. Thus, Otop1 defines a unique target of cytokine signaling that attenuates obesity-induced adipose tissue inflammation and plays an adaptive role in maintaining metabolic homeostasis in obesity.

journal_name

Diabetes

journal_title

Diabetes

authors

Wang GX,Cho KW,Uhm M,Hu CR,Li S,Cozacov Z,Xu AE,Cheng JX,Saltiel AR,Lumeng CN,Lin JD

doi

10.2337/db13-1139

subject

Has Abstract

pub_date

2014-04-01 00:00:00

pages

1340-52

issue

4

eissn

0012-1797

issn

1939-327X

pii

db13-1139

journal_volume

63

pub_type

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