Aglycin ameliorates nonalcoholic fatty liver disease through modulation of the gut microbiota, restoration of the intestinal barrier, and inhibition of hepatic inflammation in mice

Abstract

The gut microbiota plays a pivotal role in the pathogenesis of metabolic disorders such as nonalcoholic fatty liver disease (NAFLD). Aglycin, a bioactive peptide derived from soybeans, exhibits efficacy in ameliorating various metabolic disorders including diabetes; however, its role in alleviating NAFLD through modulation of the gut microbiota and the underlying mechanisms remain unclear. This study used a mouse NAFLD model induced through a high-fat, high-fructose (HFHF) diet to investigate the effects of aglycin on the gut microbiota, serum metabolites, intestinal barrier, and hepatic inflammation. Our findings indicated that aglycin reduced body weight gain, mitigated liver enzyme levels and blood lipid metabolic indices, normalized adipose tissue abnormalities, and alleviated hepatic steatosis in HFHF-fed mice through an altered gut microbiota composition, increased diversity, a reduced Firmicutes/Bacteroidetes ratio, and improved metabolite profiles. Additionally, aglycin restored intestinal barrier integrity by upregulating tight junction proteins (occludin, claudin-1 and ZO-1) and suppressed hepatic inflammation by inhibiting the TLR4/NF-κB pathway. Our findings underscore the beneficial effects of aglycin in NAFLD and provide novel insights into the prevention and treatment of this condition.