RRC ID 51631
著者 Wada T, Sunaga H, Miyata K, Shirasaki H, Uchiyama Y, Shimba S.
タイトル Aryl Hydrocarbon Receptor Plays Protective Roles against High Fat Diet (HFD)-induced Hepatic Steatosis and the Subsequent Lipotoxicity via Direct Transcriptional Regulation of Socs3 Gene Expression.
ジャーナル J Biol Chem
Abstract Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor regulating the expression of genes involved in xenobiotic response. Recent studies have suggested that AhR plays essential roles not only in xenobiotic detoxification but also energy metabolism. Thus, in this study, we studied the roles of AhR in lipid metabolism. Under high fat diet (HFD) challenge, liver-specific AhR knock-out (AhR LKO) mice exhibited severe steatosis, inflammation, and injury in the liver. Gene expression analysis and biochemical study revealed thatde novolipogenesis activity was significantly increased in AhR LKO mice. In contrast, induction of suppressor of cytokine signal 3 (Socs3) expression by HFD was attenuated in the livers of AhR LKO mice. Rescue of theSocs3gene in the liver of AhR LKO mice cancelled the HFD-induced hepatic lipotoxicities. Promoter analysis established Socs3 as novel transcriptional target of AhR. These results indicated that AhR plays a protective role against HFD-induced hepatic steatosis and the subsequent lipotoxicity effects, such as inflammation, and that the mechanism of protection involves the direct transcriptional regulation ofSocs3expression by AhR.
巻・号 291(13)
ページ 7004-16
公開日 2016-3-25
DOI 10.1074/jbc.M115.693655
PII S0021-9258(20)42954-0
PMID 26865635
PMC PMC4807284
MeSH Animals Basic Helix-Loop-Helix Transcription Factors / deficiency Basic Helix-Loop-Helix Transcription Factors / genetics* Binding Sites Diet, High-Fat* Dietary Fats / adverse effects* Fatty Liver / etiology Fatty Liver / genetics* Fatty Liver / metabolism Fatty Liver / pathology Gene Expression Regulation Lipid Metabolism Liver / metabolism Liver / pathology Male Mice Mice, Inbred C57BL Mice, Knockout Promoter Regions, Genetic Protein Binding Receptors, Aryl Hydrocarbon / deficiency Receptors, Aryl Hydrocarbon / genetics* Signal Transduction Suppressor of Cytokine Signaling 3 Protein Suppressor of Cytokine Signaling Proteins / genetics* Suppressor of Cytokine Signaling Proteins / metabolism Transcription, Genetic
IF 4.238
引用数 21
リソース情報
ヒト・動物細胞 RAW 264(RCB0535)