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      Metabolomic Profiles of Overweight/Obesity Phenotypes During Adolescence: A Cross‐Sectional Study in Project Viva

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          Abstract

          Characterize metabolomics profiles of four overweight/obese (OWOB) and metabolic risk (MetRisk) phenotypes among 524 adolescents age ~13 years. We created a four-level phenotype variable (non-OWOB & low MetRisk, non-OWOB & high MetRisk, OWOB & low MetRisk, OWOB & high MetRisk) using BMI percentile to define OWOB, and derived high vs. low MetRisk as the 4 th vs. 1 st –3 rd quartiles of a z-score calculated as the average of 5 externally-standardized z-scores for waist circumference, HOMA-IR, HDL, triglycerides, and SBP. We then examined associations of nine metabolite patterns derived from principal components analysis with phenotype after accounting for age, sex, race, and pubertal status. Five metabolite patterns differed with respect to phenotype: Factor 1 comprised long-chain fatty acids and was lower among non-OWOB & high MetRisk (−0.90 [95% CI: −1.39, −0.42]) vs. non-OWOB & low MetRisk (referent). Factors 5 (branched chain amino acids; BCAAs), 8 (diacylglycerols) and 9 (steroid hormones) were highest among OWOB & high MetRisk. Factor 7 (long-chain acylcarnitines) was higher among non-OWOB & high MetRisk (0.47 [0.04, 0.91]) and lower among OWOB & low MetRisk (−0.36 [−0.68, −0.04]). Long-chain fatty acids, BCAAs, acylcarnitines, diacylglycerols, and steroid hormones differed by weight status and metabolic phenotype.

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          Most cited references3

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          High resolution mass spectrometry improves data quantity and quality as compared to unit mass resolution mass spectrometry in high-throughput profiling metabolomics

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            The IDF consensus world-wide definition of the metabolic syndrome.

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              Carnitine metabolism in normal-weight and obese human subjects during fasting.

              Carnitine metabolism was studied in normal-weight and obese subjects by measurement of carnitine and its acyl derivatives in plasma and urine. When first fed an isocaloric, low-carnitine diet, both groups showed a decrease in plasma total carnitine, primarily due to a decrease in the free carnitine fraction. Urinary free carnitine excretion also fell significantly. When fasting was instituted, plasma total carnitine concentration increased. This was the net result of a rapid increase in short-chain and long-chain acylcarnitine and a delayed decrease in free carnitine. Urinary excretion of short-chain acylcarnitines increased parallel to rising plasma concentrations, whereas free carnitine excretion first decreased and then tended to increase slightly. Both plasma and urinary short-chain acylcarnitine correlated with beta-hydroxybutyrate. All of these changes were reversed by refeeding, in the obese even with a low-carnitine hypocaloric intake. Obese subjects also developed hyperketonemia significantly more slowly than did normal-weight subjects, yet demonstrated substantially the same changes in magnitude and direction in carnitine and its metabolites.
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                Author and article information

                Contributors
                Journal
                Obesity
                Obesity
                Wiley
                1930-7381
                1930-739X
                February 2020
                December 26 2019
                February 2020
                : 28
                : 2
                : 379-387
                Affiliations
                [1 ]Department of Epidemiology, Lifecourse Epidemiology of Adiposity and Diabetes (LEAD) Center, Colorado School of Public Health University of Colorado Denver Anschutz Medical Campus Aurora Colorado USA
                [2 ]Division of Chronic Disease Research Across the Lifecourse (CoRAL) Department of Population Medicine Harvard Medical School/Harvard Pilgrim Health Care Institute Boston Massachusetts USA
                [3 ]Diabetes Unit Massachusetts General Hospital Boston Massachusetts USA
                [4 ]Department of Nutrition T. H. Chan Harvard School of Public Health Boston Massachusetts USA
                Article
                10.1002/oby.22694
                6980913
                31876390
                f3ec65c3-3183-4e2a-9498-6ff3d106f530
                © 2020

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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