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

Katie C. Hootman, Jean Pierre Trezzi, Lisa Kraemer, Lindsay S. Burwell, Xiangyi Dong, Kristin A. Guertin, Christian Jaeger, Patrick J. Stover*, Karsten Hiller, Patricia A. Cassano

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

45 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)E4233-E4240
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number21
DOIs
Publication statusPublished - 23 May 2017

Keywords

  • Adiposity
  • Erythritol
  • Metabolomics
  • Pentose-phosphate pathway
  • Weight gain

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