I3A Improves the Hepatic Mitochondrial Respiration Defects in NAFLD Disease Model

Recent evidences have linked indole-3-acetic acid (I3A), a gut microbiota-derived metabolite from dietary tryptophan, with the resistance to liver diseases. However, data supporting I3A-mediated protection against nonalcoholic fatty liver disease (NAFLD) remain incomprehensive. In this study, we verified that I3A definitely alleviates dietary-induced metabolic impairments, particularly glucose dysmetabolism and liver steatosis. Importantly, we expand the understanding of I3A further to enhancing mitochondrial respiration complex (MRC) capacity by RNA-seq. We found that I3A restored the deficiency of MRC capacity in palmitic acid (PA)-induced HepG2 in vitro. These changes were associated with complex I and III expression and their activities. In addition, pre-treatment of I3A guard against the deficiency of not only the MRC capacity but also ATP production due to the advanced protection effect on the expression and activity of complex V. In conclusion, our findings uncover that I3A increased expression and activity of hepatic oxidative phosphorylation subunits, contributing to mitochondrial respiration improvement in NAFLD mice. Overall design: Liver mRNA profiles of HFD and HFD+I3A mice