Qualitative Properties of Circulating Fatty Acids Are Associated With MASLD: A Cross-Sectional Study From the NHANES Database

Background and Objective The role of circulating fatty acids (FA) as well as the association between their composition and metabolic dysfunction-associated steatotic liver disease (MASLD) is not known. Here, we evaluate the association between specific FA subtypes and both MASLD and liver fibrosis in a general population setting.Methods In this cross-sectional study, serum levels of FAs were measured after an overnight fast in a representative sample of the general US population. Concentrations of total FA were assessed using capillary gas chromatography coupled with negative-ion mass spectrometry. They were divided into saturated (palmitic, stearic and butyric acid), monounsaturated (palmitoleic and oleic acid), omega-6 polyunsaturated (omega-6 PUFA: linoleic and arachidonic acid) and omega-3 PUFA (alpha-linolenic, docosanoic [DHA] and eicosapentaenoic [EPA] acid). Explorative end points were: insulin resistance, liver steatosis and fibrosis estimated using the Homeostatic Model of Insulin Resistance (HOMA-IR), a fatty liver index (FLI) score >= 60 and a Fibrosis 4 (FIB-4) score >= 1.3, respectively. Logistic regression analyses were performed to assess their associations with different FAs after adjustment for confounders.Results A total of 2440 people were included in the study. Concentrations of all considered FAs increased progressively across HOMA-IR quartiles. A similar trend was identified when the population was segregated according to FLI. In logistic regression analyses adjusted for age, sex, body mass index and race-ethnicity, when evaluated as a percentage of all circulating FAs, linoleic acid, arachidonic acid and DHA were inversely associated with insulin resistance and liver steatosis. Finally, only alpha-linolenic acid was associated with a lower risk of liver fibrosis (OR: 0.48, 95% CI 0.25-0.93, p = 0.031).Conclusions This study provides initial epidemiologic evidence in humans that omega-3 PUFA in particular are associated with a lower risk of liver steatosis and alpha-linolenic acid in particular was also protective against fibrosis, supporting data in animal models. Moreover, their circulating levels might be manipulated using nutritional strategies in clinical studies.