Insulin resistance as potential mediator linking ApoB/ApoA1 to MAFLD, but not inflammation

Metabolic-associated fatty liver disease (MAFLD) is closely associated with insulin resistance (IR) and systemic inflammation. Apolipoprotein A1 (ApoA1) and Apolipoprotein B (ApoB), as notable non-traditional lipid markers, have demonstrated distinct advantages in identifying risks related to metabolic syndrome and coronary atherosclerosis, yet its association with MAFLD and the mediating roles of IR/inflammation remain unclear. This retrospective investigation involved 1061 participants, categorized into a non-MAFLD group (n = 529) and an MAFLD group (n = 532). Univariate and multivariate logistic regression models, Spearman's correlation, and mediation analysis were utilized to explore the intricate associations between ApoB/ApoA1, MAFLD, inflammation, and IR. The MAFLD group exhibited markedly elevated levels of neutrophils/lymphocytes, neutrophils/platelets, systemic immune inflammation index, systemic inflammation response index, pan-immune-inflammation value and triglyceride-glucose index (TyG), TyG body mass index (TyGBMI), and metabolic score for insulin resistance (METS-IR) compared to the non-MAFLD group. Logistic regression analysis revealed that ApoB/ApoA1, TyG, TyGBMI, and METS-IR were markedly linked to MAFLD risk. Spearman's correlation analysis identified substantial positive links between ApoB/ApoA1 and TyG (r = 0.45), METS-IR (r = 0.47), and TyGBMI (r = 0.42). Mediation analysis, adjusted for confounding variables, revealed that TyG, TyGBMI, and METS-IR mediated 70.4%, 100%, and 100% of the association between ApoB/ApoA1 and MAFLD, respectively. Our findings clarify the complex interrelationships between ApoB/ApoA1, MAFLD risk, inflammation, and IR, and for the first time, demonstrate that IR may act as a key potential mediator in the link between ApoB/ApoA1 and MAFLD, rather than systemic inflammation. This suggests that IR may serve a more prominent role than chronic systemic inflammation in the association between lipid metabolism and MAFLD risk, and intervening in IR may be more effective than anti-inflammatory therapy in blocking the progression from lipid metabolism disorders to MAFLD.