Metabolome Alterations Associated with 12-Week Sitting Time Reduction among Sedentary, Postmenopausal Latinas

Background: Prolonged sitting is associated with health risk. The metabolic impact of replacing sitting time with standing is unknown. We explored metabolome changes after a 12-week standing intervention. Methods: Sedentary postmenopausal Latinas with overweight (N=254; 55+ years of age; BMI ≥25 kg/m2) were randomized to an increased standing intervention or a health education control group. Clinical, behavioral and fasting plasma measurements were collected at baseline and 12-weeks. Sitting, standing and stepping time was assessed objectively by a thigh-worn inclinometer (activPAL). Aqueous metabolites and carnitines were measured using LC-MS/MS. Results: Top tertile of intervention group Best Responders (N=43) was selected by criteria of change in mean sitting bout duration and total sitting time. Variable-Matched Controls (N=43) were selected from the control group using a random forest model trained to predict the Best-Responders. Best Responders changed sitting and standing time by -110.0 (11.0) and 104.6 (10.1) min, respectively, compared to the Matched Controls change of 7.1 (9.8) and -7.8 (9.0) min, respectively. A covariate-controlled GLM revealed significant group differences in change scores of 24 metabolites (FDR q = 0.048-2.1E-4) from baseline to 12-week follow-up. Enzyme enrichment predicted significant functional changes in enzymes involved in glutamate and histidine catabolism. Pathway analysis showed significant effects in 14 metabolites of aminoacyl tRNA biosynthesis, as well as 4 metabolites involved in phenylalanine, tyrosine, tryptophan, ubiquinone/terpenoid-quinone biosynthesis and beta-alanine metabolism (all p < 0.05). Metabolite change scores mapped to central carbon metabolism with significant elevation of 14 amino acids involved in pyruvate, acetoacetyl- and acetyl-CoA metabolism, and TCA cycle intermediate biosynthesis. Conclusion: Standing intervention results in broad amino acid metabolism alterations. Disclosure J.Patterson: None. P.Jasbi: None. H.Gu: None. M.Allison: None. C.Reuter: None. B.Rana: None. L.Natarajan: None. D.D.Sears: None. Funding American Heart Association (16SFRN28420000)