Pasteurized Akkermansia muciniphila (p-AKK) is related to lipid metabolism and helps control obesity. The main goal of this study was to investigate the role and mechanism of p-AKK in lipid metabolism using Caenorhabditis elegans. The results showed that p-AKK increased the healthy lifespan of nematodes and helped maintain exercise ability in aging, suggesting a potential increase in energy expenditure. The overall fat deposition and triglyceride level were significantly decreased and the p-AKK anti-oxidative stress helped to regulate fatty acid composition. Additionally, the transcriptome results showed that p-AKK increased the expression of lipo-hydrolase and fatty acid β-oxidation-related genes, including lipl-4, nhr-49, acs-2 and acdh-8, while it decreased the expression of fat synthesis-related genes, including fat-7, elo-2 and men-1. These results partially explain the mechanisms underlying the fact that p-AKK decreases fat accumulation of C. elegans via nhr-49/acs-2-mediated signaling involved in fatty acid β-oxidation and synthesis.