Improve effect of Akkermansia muciniphila ONE on lipid metabolism of type 2 diabetes mice through regulating the AMPK/PPAR-α signaling pathway

Akkermansia muciniphila (AKK) exerts beneficial effects by enhancing gut health, improving metabolic parameters, and modulating inflammation, thereby potentially preventing or alleviating conditions such as obesity and T2DM. This study aimed to evaluate the effect of the AKK ONE strain on lipid metabolism in T2DM mice. The results showed that AKK ONE prevented diabetes-associated weight loss, reduced the liver index and OGTT levels, and significantly decreased serum INS, LDL-C, and AST levels, while increased GLP-1 and HDL-C levels. Histopathological analysis showed that AKK ONE alleviated hepatic steatosis and increased pancreatic islet area. At the molecular level, AKK ONE upregulated the AMPK, PPAR-α, and SREBP2 expression, and downregulated HMGCR. In vitro, AKK cell-free supernatant exhibited strong antioxidant activity, including DPPH and hydroxyl radical scavenging capacity and total antioxidant potential. These results suggest that AKK ONE and its metabolites may ameliorate T2DM-related lipid dysregulation, likely through activation of the AMPK/PPAR-α pathway and modulation of oxidative stress. • AKK ONE alleviated the damage caused by T2DM on the liver and pancreas of mice. • AKK ONE regulated the levels of lipid metabolism-related genes and proteins. • AKK cell-free supernatant showed the strongest in vitro anti-oxidant activity. • The AMPK/PPAR-α pathway could activiate by AKK and its metabolites.