1. Role of the Aryl Hydrocarbon Receptor and Gut Microbiota-Derived Metabolites Indole-3-Acetic Acid in Sulforaphane Alleviates Hepatic Steatosis in Mice
- Author
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Xin Dai, Qijin He, Chen Yan, Jingyue Zhang, Bangmao Wang, Lu Zhou, Hengjie Yuan, Maojuan Ran, Ling Liang, Lu Zhang, Xin Chen, Jie Zhang, Chenxi Lou, Siyuan Sun, Xiuxiu Xu, and Jingwen Zhao
- Subjects
medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,AHR ,sulforaphane ,Inflammation ,Gut flora ,Proinflammatory cytokine ,chemistry.chemical_compound ,Downregulation and upregulation ,Internal medicine ,NAFLD ,medicine ,TX341-641 ,Nutrition ,Original Research ,Nutrition and Dietetics ,biology ,gut microbiota ,Nutrition. Foods and food supply ,Chemistry ,food and beverages ,Lipid metabolism ,Aryl hydrocarbon receptor ,biology.organism_classification ,medicine.disease ,Endocrinology ,high-fat diet ,biology.protein ,lipids (amino acids, peptides, and proteins) ,indole-3-acetic acid ,medicine.symptom ,Steatosis ,Food Science ,Sulforaphane - Abstract
Scope: Gut microbiome-derived metabolites are the major mediators of diet-induced host-microbial interactions. Aryl hydrocarbon receptor (AHR) plays a crucial role in glucose, lipid, and cholesterol metabolism in the liver. In this study, we aimed to investigate the role of indole-3-acetic acid (IAA) and AHR in sulforaphane (SFN) alleviates hepatic steatosis in mice fed on a high-fat diet (HFD).Methods and Results: The HFD-fed male C57BL/6 mice were intervened with SFN for 6 weeks. HFD-mice showed classical pathophysiological characteristics of hepatic steatosis. The results showed that SFN significantly reduced body weight, liver inflammation and hepatic steatosis in HFD-fed mice. SFN reduced hepatic lipogenesis by activating AHR/SREBP-1C pathway, which was confirmed in HepG2 cell experiments. Moreover, SFN increased hepatic antioxidant activity by modulating Nrf-2/NQO1 expression. SFN increased serum and liver IAA level in HFD mice. Notably, SFN manipulated the gut microbiota, resulting in reducing Deferribacteres and proportions of the phylum Firmicutes/Bacteroidetes and increasing the abundance of specific bacteria that produce IAA. Furthermore, SFN upregulated Ahr expression and decreased the expression of inflammatory cytokines in Raw264.7 cells.Conclusions: SFN ameliorated hepatic steatosis not only by modulating lipid metabolism via AHR/SREBP-1C pathway but regulating IAA and gut microbiota in HFD-induced NAFLD mice.
- Published
- 2021