Sci Rep. 2026 May 6. doi: 10.1038/s41598-026-51430-0. Online ahead of print.

ABSTRACT

Metabolic dysfunction-associated fatty liver disease (MAFLD) and carotid artery plaque (CAP) are both linked to circulatory lipid and lipoprotein metabolism. However, the shared lipidome-wide mechanisms underlying these diseases remain unexplored. To identify plasma lipid species associated with both MAFLD and CAP to uncover their shared metabolic pathways. We analyzed data from the Young Finns Study cohort from the 2007 and 2018 follow-ups (n = 1496, aged 41-56 years, 56.3% females). Ultrasound was used to determine the prevalence of both CAP and MAFLD during the 2018 follow-up. The participants were categorized into three mutually exclusive groups: participants with CAP without MAFLD (n = 257), participants with MAFLD without CAP (n = 150), and a control group free from both diseases (n = 436). Lipidomic profiling of 437 lipid species from plasma was performed during the 2007 follow-up (aged 30-45 years) via liquid chromatography‒tandem mass spectrometry. Logistic regression models, both unadjusted and adjusted for age, sex, physical activity, alcohol consumption, and smoking, were used to assess lipid associations with both disease outcomes separately. Odds ratios (ORs) and confidence intervals (95% CIs) were calculated for each lipid species, and multiple testing corrections were performed via the false discovery rate (FDR) method (< 0.05). Additionally, we performed a hypergeometric enrichment analysis to determine whether certain lipid classes appear more often than expected among the lipids associated with disease. In the unadjusted models, there were a total of 51 significant (FDR < 0.05) overlapping lipids between the CAP and MAFLD groups. In the adjusted models, four lipids were significantly associated with CAP, and 202 lipids were significantly associated with MAFLD. Notably, only one lipid-phosphatidylcholine (PC) 40:4-was significantly associated with both diseases. PC 40:4 was associated with an increased risk of CAP (OR 2.59; 95% CI, 1.57-4.32) and MAFLD (OR 5.26; 95% CI, 2.81-9.85). Our findings highlight PC 40:4 as a novel shared lipid signature for both MAFLD and CAP. This dual association suggests that overlapping metabolic disturbances and potentially common lipid-based pathogenic mechanisms link liver and vascular health. PC 40:4 may serve as a promising early biomarker or therapeutic target for metabolic-vascular comorbidities.

PMID:42092119 | DOI:10.1038/s41598-026-51430-0