ArticleJournal of inflammation research2025
The Protective Effect of Bilirubin on MAFLD May Be Mediated by Improving Insulin Re-Sistance and Alleviating Chronic Inflammation.
Article in Journal of inflammation research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed.
- Bilirubin reduces mortality in sepsis models by inhibiting NOX2-mediated formation of neutrophil extracellular traps.Redox report : communications in free radical research · 2026Article
- Association between total bilirubin levels and the risk of acute kidney injury: a large hospital- based cohort study.BMC nephrology · 2026Article
- Exercise attenuates high-fat diet-induced liver injury in mice via PPARα pathway and reduction of oxidative stress and inflammation.Journal of physiology and biochemistry · 2026Article
- Metabolic characteristics and factors associated with prediabetes in Chinese adults based on real-world health examination data: a cross-sectional study.Frontiers in nutrition · 2026Article
- Effects of maternal overnutrition and metabolic challenge in adult life on the histological integrity of the liver and intestinal epithelium in rabbits.Frontiers in nutrition · 2025Article
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Bilirubin, as a potent endogenous antioxidant, has demonstrated protective effects in various metabolic and inflammatory diseases. However, the precise role and underlying mechanisms of bilirubin in metabolic-associated fatty liver disease (MAFLD) remain unclear. Methods: This study involved 3000 participants, categorized into non-MAFLD and MAFLD groups. Using weighted multiple linear regression and mediation effect analysis, this study examined the protective impact of total bilirubin (TBIL), direct bilirubin (DBIL), and indirect bilirubin (IBIL) on MAFLD risk. Additionally, potential mediators-inflammation and insulin resistance (IR) through which bilirubin exerts its protective effects were explored. Results: TBIL and DBIL levels in the MAFLD group were significantly lower than those in the non-MAFLD group. Multiple linear regression analysis, adjusted for confounding variables, revealed that compared to the lowest tertile group (TBIL < 14.6), the odds ratios (ORs) for the middle tertile (TBIL 14.6-19.2) and the highest tertile (TBIL ≥ 19.3) groups were 0.735 and 0.615. Similarly, compared to the lowest tertile group (DBIL < 3.4), the ORs for the middle tertile (DBIL 3.4-4.4) and the highest tertile (DBIL ≥ 4.5) groups were 0.613 and 0.367. Mediation analysis revealed significant indirect effects of SIRI, PIV, TyG, TyGBMI, METS-IR, and AIP on the relationship between TBIL, DBIL, and MAFLD risk. Specifically, SIRI mediated 4.07% and 1.55% of the TBIL-MAFLD and DBIL-MAFLD associations, respectively; PIV mediated 9.56% and 4.22%; TyG mediated 69.27% and 81.91%; TyGBMI mediated 100% and 78.34%; METS-IR mediated 100% and 81.41%; and AIP mediated 100% for both TBIL-MAFLD and DBIL-MAFLD associations. Conclusion: Our findings suggest that increased serum levels of TBIL and DBIL are significantly inversely correlated with MAFLD risk, with both serving as independent protective factors against MAFLD occurrence. Further mediation analysis indicates that this protective effect is likely mediated by improvements in IR and the alleviation of systemic chronic inflammation.
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