Xiang Liu, Fei Men
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading chronic liver disease worldwide. While total SFA intake has been linked to MASLD, the contribution of specific SFA and the mechanism underlying the SFA-MASLD association remain unclear. This study evaluated the associations of individual SFA with MASLD and the mediating roles of insulin resistance (IR) and serum albumin. We used data from seven National Health and Nutrition Examination Survey (NHANES) cycles (2005-2018) in a cross-sectional analysis. Associations between individual SFA and MASLD were estimated via logistic regression with restricted cubic splines (RCS). Weighted quantile sum (WQS) and quantile g-computation (QGC) models assessed the mixture associations. Mediation analysis evaluated the proportions of these associations accounted for by serum albumin and IR. Compared with the reference group, the highest tertile of intake was associated with increased odds of MASLD for C4:0 (OR = 1·12, 95 % CI 1·01, 1·25), C6:0 (OR = 1·15, 95 % CI 1·04, 1·28), C14:0 (OR = 1·20, 95 % CI 1·08, 1·33), C16:0 (OR = 1·24, 95 % CI 1·12, 1·38) and C18:0 (OR = 1·25, 95 % CI 1·12, 1·39). RCS models revealed largely linear dose-response relationships. Both WQS and QGC indicated a positive joint association of SFA with MASLD, with C16:0 identified as a major contributor. Among SFA significantly associated with MASLD, IR accounted for 30·0-47·4 % of the associations, while serum albumin accounted for 5·9-8·0 %. Higher intakes of short- and long-chain SFA, both individually and collectively, are associated with higher odds of MASLD. IR and serum albumin may partially explain these associations. These findings support the development of precision dietary strategies targeting specific SFA for MASLD prevention.