2111-P: Effect Modification of Vitamin D Intervention by Obesity-Related Metabolites

Background: Effects of vitamin D on biomarkers of cardiometabolic disorders among obese individuals are highly variable between studies. Comparing the effects of vitamin D supplementation in metabolically healthy (MHO) vs. metabolically unhealthy (MUHO) obesity using metabolomics may yield mechanistic insights into the observed heterogeneity. Objective: To quantify small molecular changes shortly after vitamin D intervention in MHO and MUHO individuals with sub-optimal levels of vitamin D ( Methods: In two randomized double-blind clinical trials, 110 MHO and 105 MUHO individuals were separately and randomly assigned to receive a daily dose of vitamin D supplement (4000 IU) or placebo. These MHO/MUHO phenotypes were defined using the Adult Treatment Panel-III criteria. Obesity-related metabolites (n=104) were measured at baseline and after four months of supplementation, using liquid chromatography coupled to a triple quadrupole mass spectrometry. Multiple linear regression models were fit to assess changes in metabolite levels, adjusting for appropriate covariates as well as controlling for multiple testing. Results: In the MUHO group (n=78), we identified ten metabolites (citrulline, acyl-lysophosphatidylcholines C16:0, C16:1, C18:0 and C18:1, diacyl-phosphatidylcholines C32:0, C34:1, C38:3 and C38:4 and sphingomyelin C40:4) that were significantly altered (P=4.9×10-4 to P=0.007) in response to vitamin D therapy. In the MHO group (n=82), no significant metabolite changes were observed after the intervention. Conclusion: Findings from our study contribute to the understanding of biological variation in Vitamin D metabolism across different obesity phenotypes. Upon successful validation, these insights can increase precision of clinical approaches to metabolic derangements in obesity. This study was registered at www.irct.ir as IRCT2015061522762N1. Disclosure M. Bagheri: None. S. Aslibekyan: Employee; Self; 23andMe. A. Djazayery: None. F. Farzadfar: None. Funding Tehran University of Medical Sciences