Potential mediation effect of insulin resistance on the association between iron metabolism indicators and non-alcoholic fatty liver disease

ObjectivesIron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). However, the interplay between them on the occurrence and progression of NAFLD is not fully understood. We aimed to disentangle the crosstalk between iron metabolism and IR and explore its impact on NAFLD.MethodsWe analyzed data from the National Health and Nutritional Examination Survey (NHANES) 2017-2018 to evaluate the association between serum iron metabolism indicators (ferritin, serum iron, unsaturated iron-binding capacity [UIBC], total iron-binding capacity [TIBC], transferrin saturation, and transferrin receptor) and NAFLD/non-alcoholic steatohepatitis (NASH). Mediation analysis was conducted to explore the role of IR played in these relationship.ResultsA total of 4812 participants were included, among whom 43.7% were diagnosed with NAFLD and 13.2% were further diagnosed with NASH. After adjusting the covariates, the risk of NAFLD increases with increasing serum ferritin (adjusted odds ratio [aOR] 1.71, 95% confidence interval [CI] 1.37-2.14), UIBC (aOR 1.45, 95% CI 1.17-1.79), and TIBC (aOR 1.36, 95% CI 1.11-1.68). Higher levels of serum ferritin (aOR 3.70, 95% CI 2.25-6.19) and TIBC (aOR 1.69, 95% CI 1.13-2.56) were also positively associated with NASH. Participants with IR were more likely to have NAFLD/NASH. Moreover, IR-mediated efficacy accounted for 85.85% and 64.51% between ferritin and NAFLD and NASH, respectively.ConclusionHigher levels of serum ferritin and TIBC are closely associated with the occurrence of NAFLD and NASH. IR may be considered a possible link between NAFLD or NASH and increased serum ferritin levels. Iron metabolism and insulin resistance (IR) are closely related to non-alcoholic fatty liver disease (NAFLD). In this study we used population data to investigate the complex crosstalk between serum iron metabolism indicators and IR in the pathogenesis of NAFLD. We found that increased levels of serum ferritin and total iron-binding capacity (TIBC) were closely associated with NAFLD and non-alcoholic steatohepatitis (NASH). IR might be considered a possible mediator between NAFLD/NASH and increased ferritin levels. image