Circulating Metabolite Profiles of Diet Patterns in South Asians in the United States

Abstract Objectives South Asians are at higher risk for cardiometabolic disease than many other racial/ethnic minority groups. Diet patterns in U.S. South Asians have unique components that have been associated with cardiometabolic disease. We aimed to characterize the metabolites associated with three representative diet patterns. Methods Sample: 717 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort study aged 40–84 years without known cardiovascular disease. Specimens: Fasting serum specimens and diet and demographic questionnaires at baseline. Metabolomics: LC-MS-based untargeted metabolomic and lipidomic analysis was conducted followed by targeted integration and reporting of known metabolite and lipid signals. Statistical analysis: Linear regression models of diet pattern factor score and log-transformed metabolites adjusted for age, sex, caloric intake and body mass index. Elastic net linear regression of significant metabolites. Results There were 258 metabolites with detectable signal in >98% of all serum samples. Five acylcarnitines, ten amino acids and 34 lipids were associated with greater consumption of the Animal protein (AP) pattern, and the most significant hits were trigonelline (−0.16 [−0.19, −0.12]), proline betaine (−0.12 [−0.17, −0.06]) and FA (22:6) (0.15 [0.13, 0.17]. Two acylcarnitines and 18 lipids were associated with the Fried snacks, sweets, high-fat dairy pattern (FSD), of which the top two metabolites were very long-chain unsaturated fatty acids FA (22:6) (−0.16 [−0.17, −0.10]) and FA (20:5) (−0.13, [−0.17, −0.09). There were no significant associations with the Fruits, vegetables, nuts and legumes pattern (FVNL) [false discovery rate < 0.05]. There were 29 metabolites associated with AP (R2 = 0.46) and 14 metabolites with FSD (R2 = 0.08) found with an elastic net model. Conclusions The AP and FSD patterns in U.S. South Asians are associated with metabolite expression patterns differing predominantly in amino acid and omega-3 unsaturated fatty acids. These findings will inform future investigation on associations with incident diabetes and cardiovascular disease and mechanisms of prevention in this high-risk population. Funding Sources NIDDK, NHLBI.