Nuclear Orphan Receptor TAK1/TR4-Deficient Mice Are Protected Against Obesity-Linked Inflammation, Hepatic Steatosis, and Insulin Resistance

• DOI: 10.2337/db10-0628
• Publication Date: 2010-09-24T00:58:54Z
• Authors: Hong Soon Kang; Kyoko Okamoto; Yong-Sik Kim; Yukimasa Takeda; Carl D. Bortner; Huaixin Dang; Taira Wada; Wen Xie; Xiao-Ping Yang; Grace Liao; Anton M. Jetten
• Keywords: Steatosis; CD36

The nuclear receptor TAK1/TR4/NR2C2 is expressed in several tissues that are important the control of energy homeostasis. In this study, we investigate whether TAK1 functions as a regulator lipid and homeostasis has role metabolic syndrome.We generated TAK1-deficient (TAK1⁻(/)⁻) mice to study function development syndrome aged fed high-fat diet (HFD). (Immuno)histochemical, biochemical, gene expression profile analyses were performed determine effect loss on liver adipose tissues. addition, insulin sensitivity, expenditure, adipose-associated inflammation compared wild-type (WT) TAK1⁻(/)⁻ HFD.TAK1-deficient resistant age- HFD-induced syndrome. Histo- biochemical showed significantly lower hepatic triglyceride levels reduced accumulation tissue with WT mice. Gene profiling analysis revealed genes encoding proteins involved uptake synthesis storage, including Cidea, Cidec, Mogat1, CD36, was greatly decreased primary hepatocytes Restoration induced lipogenic genes. Moreover, exhibited infiltration inflammatory cells white tissue, glucose intolerance resistance. consume more oxygen produce carbon dioxide than mice, suggesting increased expenditure.Our data reveal plays critical regulation homeostasis, promotes may provide new therapeutic target management obesity, diabetes, steatosis.