2080-LB: Metabolite Profiles of Liver Fat and BMI in the MultiEthnic Study of Atherosclerosis (MESA) and Mediators of Atherosclerosis in South Asians Living in America (MASALA) Studies

Introduction: Hepatic steatosis occurs across the body mass index (BMI) spectrum. We aimed to identify a metabolite signature for hepatic steatosis and BMI in a diverse population. Methods: We included participants from the MESA (n=1,226) and MASALA (N=668) cohorts with untargeted LC-MS metabolomics and abdominal computed tomography data at baseline, excluding those with cirrhosis, prevalent HIV, alcohol use > 14 drinks/week or routine use of steatosis-inducing medications. There were 143 concordant metabolites between two cohorts. Log-transformed and mean-centered metabolites were used for elastic net regularized regression to select an optimal subset associated with inverse hepatic attenuation or BMI, adjusted for age, gender and BMI for hepatic steatosis analysis. Results: There were 185 (10%) participants with hepatic steatosis, of which 48% were women, mean BMI 31 kg/m2 and 26% had prevalent diabetes. In elastic net analyses, 30 metabolites were selected for BMI, and 25 metabolites for intrahepatic fat with 6 in common. (Table) Conclusions: Circulating triglycerides and lower lysophosphatidylcholines were predominant for hepatic steatosis while medium and long-chain acylcarnitines were related to BMI, suggesting differences in glucose and fat metabolism, respectively, between these states of excess adiposity. M.D. Gadgil: Stock/Shareholder; LumosFit. B.M. Stroebel: None. A.M. Kanaya: None. A. Wood: Research Support; Beef Checkoff. Consultant; The Lundquist Institute. X. Guo: None. J.I. Rotter: None. P. Greenland: None. D.M. Herrington: None. NIH-NIDDKK (23DK119404), NIH-NHLBI (R01HL093009), NCATS (UL1RR024131). COMBI-BIO Research supported by EU COMBI-BIO project (FP7, 305422), and NIH/NHLBI (R01HL133932). NIH-NHLBI contracts (75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168 and N01-HC-95169). NCATS grants (UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420).