The microbiota-dependent tryptophan metabolite alleviates high-fat diet-induced insulin resistance through the hepatic AhR/TSC2/mTORC1 axis.

ABSTRACT: Type 2 diabetes (T2D) is potentially linked to disordered tryptophan metabolism that attributes to the intricate interplay among diet, gut microbiota, and host physiology. However, underlying mechanisms are substantially unknown. Comparing the gut microbiome and metabolome differences in mice fed a normal diet (ND) and high-fat diet (HFD), we uncover that the gut microbiota-dependent tryptophan metabolite 5-hydroxyindole-3-acetic acid (5-HIAA) is present at lower concentrations in mice with versus without insulin resistance. We further demonstrate that the microbial transformation of tryptophan into 5-HIAA is mediated by Burkholderia spp. Additionally, we show that the administration of 5-HIAA improves glucose intolerance and obesity in HFD-fed mice, while preserving hepatic insulin

SUBMITTER: Du W 

PROVIDER: S-EPMC11363250 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature