PLoS ONE (Jan 2014)

Improved metabolic health alters host metabolism in parallel with changes in systemic xeno-metabolites of gut origin.

  • Caitlin Campbell,
  • Dmitry Grapov,
  • Oliver Fiehn,
  • Carol J Chandler,
  • Dustin J Burnett,
  • Elaine C Souza,
  • Gretchen A Casazza,
  • Mary B Gustafson,
  • Nancy L Keim,
  • John W Newman,
  • Gary R Hunter,
  • Jose R Fernandez,
  • W Timothy Garvey,
  • Mary-Ellen Harper,
  • Charles L Hoppel,
  • John K Meissen,
  • Kohei Take,
  • Sean H Adams

DOI
https://doi.org/10.1371/journal.pone.0084260
Journal volume & issue
Vol. 9, no. 1
p. e84260

Abstract

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Novel plasma metabolite patterns reflective of improved metabolic health (insulin sensitivity, fitness, reduced body weight) were identified before and after a 14-17 wk weight loss and exercise intervention in sedentary, obese insulin-resistant women. To control for potential confounding effects of diet- or microbiome-derived molecules on the systemic metabolome, sampling was during a tightly-controlled feeding test week paradigm. Pairwise and multivariate analysis revealed intervention- and insulin-sensitivity associated: (1) Changes in plasma xeno-metabolites ("non-self" metabolites of dietary or gut microbial origin) following an oral glucose tolerance test (e.g. higher post-OGTT propane-1,2,3-tricarboxylate [tricarballylic acid]) or in the overnight-fasted state (e.g., lower γ-tocopherol); (2) Increased indices of saturated very long chain fatty acid elongation capacity; (3) Increased post-OGTT α-ketoglutaric acid (α-KG), fasting α-KG inversely correlated with Matsuda index, and altered patterns of malate, pyruvate and glutamine hypothesized to stem from improved mitochondrial efficiency and more robust oxidation of glucose. The results support a working model in which improved metabolic health modifies host metabolism in parallel with altering systemic exposure to xeno-metabolites. This highlights that interpretations regarding the origins of peripheral blood or urinary "signatures" of insulin resistance and metabolic health must consider the potentially important contribution of gut-derived metabolites toward the host's metabolome.