The Role of Insulin Resistance in Mediating the Association Between Proinflammatory Diets and Metabolic Dysfunction-Associated Steatotic Liver Disease.

The association between proinflammatory dietary patterns and metabolic dysfunction-associated steatotic liver disease (MASLD) has been increasingly recognized; however, the underlying biological mechanisms remain unclear. This study aimed to investigate the relationship between dietary inflammatory potential and MASLD risk and to evaluate the mediating role of insulin resistance (IR)-related biomarkers in this association. A total of 13,675 participants from the National Health and Nutrition Examination Survey were included. Dietary inflammatory potential was assessed using the Dietary Inflammatory Index (DII) and Food Inflammatory Index (FII). Insulin resistance was evaluated using the triglyceride-glucose (TyG) index and its anthropometric-adjusted derivatives, including TyG-BMI, TyG-WC, TyG-WHtR, and TyG-ABSI. Multivariable logistic regression models were applied to examine the associations between DII, FII, and MASLD risk, and mediation analyses were conducted to quantify the proportion of the associations explained by IR-related biomarkers. Participants with MASLD exhibited significantly higher DII and FII scores than those without MASLD (p < 0.001). After adjustment for potential confounders, both DII (OR = 1.07, 95% CI: 1.04-1.10) and FII (OR = 1.04, 95% CI: 1.02-1.06). were independently associated with increased MASLD risk. Furthermore, both dietary inflammatory indices were positively associated with all evaluated IR-related biomarkers. Mediation analyses demonstrated that IR significantly mediated the association between proinflammatory dietary patterns and MASLD, with TyG-WHtR showing the strongest mediating effect, accounting for 73.9% of the association between DII and MASLD and 61.5% of the association between FII and MASLD. These findings indicate that a proinflammatory dietary pattern is associated with an increased risk of MASLD and that insulin resistance may represent a key pathway linking dietary inflammatory exposure to MASLD development. The results highlight the potential importance of targeting diet-induced insulin resistance for MASLD prevention and management.