Erythritol is a pentose-phosphate pathway metabolite and associated with adiposity gain in young adults

Abstract

Metabolomic markers associated with incident central adiposity gain were investigated in young adults. In a 9-mo prospective study of university freshmen (n = 264). Blood samples and anthropometry measurements were collected in the first 3 d on campus and at the end of the year. Plasma from individuals was pooled by phenotype [incident central adiposity, stable adiposity, baseline hemoglobin A1c (HbA1c) > 5.05%, HbA1c < 4.92%] and assayed using GC-MS, chromatograms were analyzed using MetaboliteDetector software, and normalized metabolite levels were compared using Welch's t test. Assays were repeated using freshly prepared pools, and statistically significant metabolites were quantified in a targeted GC-MS approach. Isotope tracer studies were performed to determine if the potential marker was an endogenous human metabolite in men and in whole blood. Participants with incident central adiposity gain had statistically significantly higher blood erythritol [P < 0.001, false discovery rate (FDR) = 0.0435], and the targeted assay revealed 15-fold [95% confidence interval (CI): 13.27, 16.25] higher blood erythritol compared with participants with stable adiposity. Participants with baseline HbA1c > 5.05% had 21-fold (95% CI: 19.84, 21.41) higher blood erythritol compared with participants with lower HbA1c (P < 0.001, FDR = 0.00016). Erythritol was shown to be synthesized endogenously from glucose via the pentose-phosphate pathway (PPP) in stable isotope-assisted ex vivo blood incubation experiments and through in vivo conversion of erythritol to erythronate in stable isotope-assisted dried blood spot experiments. Therefore, endogenous production of erythritol from glucose may contribute to the association between erythritol and obesity observed in young adults.erythritol | metabolomics | pentose-phosphate pathway | adiposity | weight gain I n the fall of 2015, an estimated 3.3 million high-school graduates enrolled in postsecondary education as first-time college freshmen (1), and the transition to a residential college environment is associated with weight gain. About 75% of the population experiences weight gain during this transition (2, 3), but there have been few efforts to identify biomarkers of risk that could guide prevention efforts. A study (4) in monozygotic twins discordant for body mass index (BMI) reported divergence at about the age of 18 y, corresponding to a time in life when the environment shifts, and further underscoring the importance of young adulthood in the lifetime trajectory of adiposity and as a window of opportunity for prevention (5).Observational studies of young adults focus on behavioral/environmental risk factors for adiposity gain, with few studies reporting biological markers in relation to either cross-sectional and/or longitudinal changes in adiposity or body weight. A recent overview of intervention studies to prevent weight gain in young adults (6) identified 37 studies; the majority assessed diet, physical activity, and behaviors, with only 10 studies directly measuring change...

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