Plasma signature metabolites of dietary fat intake characterize associations with prevalent metabolic syndrome

Abstract The metabolic response to dietary fat intake and its relation with metabolic syndrome (MetS) remains unclear. Here, we identified dietary fat related signature metabolites and characterized their associations with MetS prevalence. We enrolled 236 participants from the Precision Nutrition and Food Safety for Dietary Prevention of Chronic Disease study in China. Nontargeted metabolomics was conducted to investigate plasma metabolome. The signature metabolites in relation to dietary fat intake were assessed using elastic net regression with a 10‐fold cross‐validation. We identified multi‐metabolite profiles comprising of 28, 19, 23, 31, and 25 metabolites, which were robustly correlated with dietary intake of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (PUFAs), n − 3 PUFAs, and n − 6 PUFAs, respectively ( r = .47–.54; p < .001). After adjustment for potential risk factors, metabolic signatures of PUFAs and n − 3 PUFAs were inversely associated with 31% and 48% lower MetS prevalence, respectively. Dietary intake of n − 3 and n − 6 PUFAs ameliorates key metabolites involved in the glyoxylate and dicarboxylate metabolism, arginine biosynthesis, and tricarboxylic acid cycle. Our findings revealed plasma metabolic signatures characterizing dietary fat intake and supported the beneficial role of PUFAs especially n − 3 PUFAs in MetS prevention.