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Indole alleviates nonalcoholic fatty liver disease in an ACE2-dependent manner.
Gao, Yuanyuan; Chen, Qi; Yang, Songtao; Cao, Jie; Li, Fangyu; Li, Rui; Wu, Zhuoying; Wang, Ying; Yuan, Li.
Afiliación
  • Gao Y; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Chen Q; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Yang S; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Cao J; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Li F; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Li R; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Wu Z; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Wang Y; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Yuan L; Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
FASEB J ; 38(18): e70061, 2024 Sep 30.
Article en En | MEDLINE | ID: mdl-39305120
ABSTRACT
Indole is a microbial metabolite produced by the gut microbiota through the degradation of dietary tryptophan, known for its well-established anti-inflammatory and antioxidant properties. In this study, we collected fecal samples from mice fed a high-fat diet (HFD) and those on a standard diet (SD), then conducted 16S rRNA sequencing to analyze their gut microbiota. The analysis revealed distinct differences in the dominant bacterial species between the two groups, with a significant decrease in indole-producing probiotics in the HFD mice compared to the SD group. Then we administered oral indole treatment to male C57BL/6J mice with HFD-induced NAFLD and observed a significant improvement in hepatic steatosis and inflammation. Notably, indole alleviated the HFD-induced decline in serum Angiotensin-(1-7) [Ang-(1-7)] levels and Angiotensin-Converting Enzyme 2 (ACE2) expression. To further investigate the role of indole and ACE2 in NAFLD, we conducted experiments using ACE2 knockout (ACE2KO) mice that were also induced with HFD-induced NAFLD and treated with indole. Interestingly, the protective effects of indole were compromised in the absence of ACE2. In HepG2 cells, indole similarly stimulated ACE2 expression and, in an ACE2-dependent manner, reduced ROS generation, maintained mitochondrial membrane potential stability, and increased SIRT3 expression. In summary, our results highlight the formation of a biologically active gut-liver axis between the gut microbiota and the liver through the tryptophan metabolite indole, which mitigates NAFLD in an ACE2-dependent manner. Elevating dietary tryptophan and increasing indole levels may represent an effective approach for preventing and treating NAFLD.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dieta Alta en Grasa / Enfermedad del Hígado Graso no Alcohólico / Microbioma Gastrointestinal / Enzima Convertidora de Angiotensina 2 / Indoles / Ratones Endogámicos C57BL Límite: Animals / Humans / Male Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dieta Alta en Grasa / Enfermedad del Hígado Graso no Alcohólico / Microbioma Gastrointestinal / Enzima Convertidora de Angiotensina 2 / Indoles / Ratones Endogámicos C57BL Límite: Animals / Humans / Male Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos