Interferon regulatory factor 3 constrains IKKβ/NF-κB signaling to alleviate hepatic steatosis and insulin resistance

• DOI: 10.1002/hep.26751
• Publication Date: 2013-10-12T01:40:12Z
• Authors: Xin-An Wang; Ran Zhang; Zhi-Gang She; Xiao-Fei Zhang; Ding-Sheng Jiang; Tao Wang; Lu Gao; Wei Deng; Shu-Min Zhang; Li-Hua Zhu; Sen Guo; Ke Chen; Xiao-Dong Zhang; De-Pei Liu; Hongliang Li
• Keywords: IRF3; Steatosis; IκB kinase

Obesity and related metabolic diseases associated with chronic low-grade inflammation greatly compromise human health. Previous observations on the roles of interferon regulatory factors (IRFs) in regulation metabolism prompted investigation involvement a key family member, IRF3, disorders. IRF3 expression liver is decreased animals diet-induced genetic obesity. The global knockout (KO) significantly promotes high-fat diet (HFD)-induced hepatic insulin resistance steatosis; contrast, adenoviral-mediated overexpression preserves glucose lipid homeostasis. Furthermore, systemic inflammation, which increased KO mice, attenuated by IRF3. Importantly, inhibitor nuclear factor kappa B kinase beta subunit / (IKKβ/NF-κB) signaling repressed κB-α (IκBα) reverses HFD-induced steatosis mice. Mechanistically, interacts domain IKKβ cytoplasm inhibits its downstream signaling. Moreover, deletion region responsible for IRF3/IKKβ interaction capacity to preserve Conclusion: inhibit IKKβ/NF-κB signaling, thus alleviating resistance, steatosis. (Hepatology 2014;59:870–885)