Long-chain omega-3-enriched erythrocyte fatty acid pattern is associated with lower odds of obesity and metabolic dysfunction-associated steatotic liver disease

Erythrocyte membrane fatty acids (FAs) reflect medium-term FA status and may capture integrated metabolic profiles beyond individual FAs. Their relationships with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD) remain insufficiently characterized. We analyzed nationally representative U.S. adults with available erythrocyte FA measurements. Principal component analysis (PCA) was applied to 21 FAs, and the first five components were retained. Survey-weighted regression models evaluated associations of principal component (PC) scores with body weight status and MASLD defined by vibration-controlled transient elastography and cardiometabolic criteria. Pearson correlations assessed relationships between PC scores and energy-adjusted dietary FA intake. False discovery rate (FDR) correction was applied. Among 4,979 adults, a long-chain omega-3-enriched pattern (PC2) was independently associated with lower odds of obesity (OR per 1-SD increase 0.74; 95% CI 0.68–0.81; q < 0.001) and was modestly correlated with higher dietary long-chain omega-3 intake ( r = 0.22). Among 3,448 participants with valid elastography data, PC2 was similarly associated with lower odds of MASLD (OR per 1-SD increase 0.73; 95% CI 0.67–0.80; q < 0.001). PC3, characterized by higher eicosadienoic acid, gondoic acid, and linoleic acid, was also inversely associated with both obesity and MASLD. In this cross-sectional study of U.S. adults, a long-chain omega-3-enriched erythrocyte FA pattern was associated with 26% lower odds of obesity and 27% lower odds of MASLD. These findings suggest that erythrocyte FA patterns may reflect integrated dietary and metabolic FA status associated with obesity and MASLD.