Chondroitin sulfate stimulates the secretion of H2S by Desulfovibrio to improve insulin sensitivity in NAFLD mice

Abstract

Hydrogen sulfide (H₂S) is a bioactive gas regulating insulin secretion and sensitivity, produced by sulfate-reducing bacteria in the gut. The present study investigated the effect of chondroitin sulfate (CS) treatment, which indirectly increased the H₂S production on nonalcoholic fatty liver disease (NAFLD). A 7-week CS supplementation had beneficial effects on body weight gain, liver function, hepatic histology, and serum lipid levels. CS could ameliorate diet-induced insulin resistance and improve insulin sensitivity via the AKT pathway, and modulate gut microbiota composition, especially increased the abundance of Desulfovibrio and elevated levels of hydrogen sulfide (H₂S). Collectively, these findings suggested that CS treatment was positively correlated with Desulfovibrio in the gut, and the metabolic H₂S flowed into the liver via the gut-liver axis, thereby triggering the AKT signaling pathway and improving insulin resistance. Thus, CS-induced alterations in the gut microbiota seem a promising for ameliorating NAFLD.

Keywords: Chondroitin sulfate; Desulfovibrio; Gut-liver axis; Hydrogen sulfide; Insulin resistance; NAFLD.