The role of AhR on HFD-induced hepatic lipotoxicity

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860088
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Environmental and hygienic pharmacy
• Research Institution: Nihon University
• Principal Investigator: WADA Taira 日本大学, 薬学部, 助教 (20597398)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: AhR / SOCS3 / NASH

Outline of Final Research Achievements

Aryl hydrocarbon receptor (AhR) is a ligand-activated transcriptional factor regulating the expression of genes involved in xenobiotic response. Recent studies have suggested that AhR plays essential roles in not only 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-knockout (AhR LKO) mice exhibited severe steatosis, inflammation, and injury in the liver. Induction of suppressor of cytokine signal 3 (Socs3) expression by HFD was attenuated in the livers of AhR LKO mice. Rescue of the Socs3 gene in the liver of AhR LKO mice cancelled the HFD-induced hepatic lipotoxicities. These results indicated that AhR plays protective roles against HFD-induced hepatic steatosis and the subsequent lipotoxicity effects, such as inflammation, and that the mechanism of the protection involves the direct transcriptional regulation of Socs3 expression by AhR.

Free Research Field

内分泌・代謝