Metabolic traits as mediators between excess salt intake and the risk of nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) affects approximately 25% of individuals worldwide and poses a significant burden on global health. In this study, we conducted Mendelian randomization analysis using salt added to food (SAF) as the exposure and investigated 249 metabolic traits as potential mediating factors. We applied multiple methods, including inverse-variance-weighted, weighted median, and Mendelian randomization-Egger, to assess causal relationships and detect pleiotropy. Mediation analysis was conducted to identify potential mediators between SAF and NAFLD. Our analysis revealed that higher SAF is associated with an increased risk of NAFLD (beta = 0.38, P = .0056). We identified 6 metabolites associated with SAF. Additionally, we found 106 metabolites associated with NAFLD. Acetate levels were identified as the primary mediator between SAF and NAFLD, mediating approximately 28.08% of the effect. Our study elucidates potential mechanisms by which excessive salt intake increases the risk of NAFLD, highlighting the role of acetate levels as a key mediator. These findings contribute to our understanding of the relationship between salt intake and NAFLD and may inform strategies for prevention and treatment. However, further research is warranted to validate these findings and explore additional mediators and mechanisms involved.