Abstract

Introduction: Sedentary behavior is associated with cardiometabolic risk independent of physical activity, but the underlying mechanisms are not fully understood. Hypothesis: Sedentary behavior may influence serum metabolite profiles which are associated with cardiometabolic risk factors. Methods: The analyses included 2711 participants (43% men) of the HCHS/SOL aged 18 to 74 years, free of CVD and other major chronic diseases. Serum metabolomics was performed using an untargeted approach. Physical activity and sedentary behavior were measured by accelerometer (Actical) for a 7-day period. Survey linear regressions were used to examine associations between sedentary behavior and metabolites. Metabolite scores were calculated by summing up z-scores of significant metabolites within the same sub-pathway. Results: Of 624 known metabolites, 95 were significantly associated with sedentary behavior ( P <0.05 after FDR correction), adjusting for socioeconomic and lifestyle factors including moderate to vigorous physical activity ( Figure 1A ). The majority of significant metabolites were clustered into 7 sub-pathways. Three sub-pathway scores (branched-chain amino acids [BCAA], acylcarnitine and medium-chain fatty acid metabolism) were positively associated with sedentary behavior, while the other 4 sub-pathway scores (acylcholine, plasmalogen, nicotinate, and arginine) were inversely associated with sedentary behavior. Among these scores, the BCAA score showed unfavorable correlations with all cardiometabolic traits including obesity measures, glycemic traits, blood lipids and blood pressure. The acylcholine score showed favorable correlations with obesity measures and glycemic traits, though positive correlations with blood lipids were observed ( Figure 1B) . Conclusions: Our study identified multiple serum metabolites associated with sedentary behavior independent of physical activity, suggesting potential mechanistic links between sedentary behavior and cardiometabolic diseases.

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