Otopetrin 1 protects mice from obesity-associated metabolic dysfunction through attenuating adipose tissue inflammation
| Autor: | Carey N. Lumeng, Maeran Uhm, Kae Won Cho, Siming Li, Alan R. Saltiel, Chun-Rui Hu, Acer E. Xu, Jiandie D. Lin, Ji-Xin Cheng, Zoharit Cozacov, Guoxiao Wang |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty FGF21 Endocrinology Diabetes and Metabolism Adipose tissue macrophages medicine.medical_treatment Adipose Tissue White Adipose tissue Inflammation White White adipose tissue Biology Diet High-Fat Pathophysiology Medical and Health Sciences Proinflammatory cytokine 03 medical and health sciences Mice Interferon-gamma Endocrinology & Metabolism 0302 clinical medicine Internal medicine Internal Medicine medicine Animals Homeostasis Obesity 030304 developmental biology 0303 health sciences Membrane Proteins Diet High-Fat Endocrinology Cytokine STAT1 Transcription Factor Adipose Tissue Tumor necrosis factor alpha medicine.symptom Insulin Resistance 030217 neurology & neurosurgery |
| Zdroj: | Diabetes, vol 63, iss 4 Diabetes |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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