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

Academic Article

Abstract

  • 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.
  • Published In

  • PLoS ONE  Journal
  • Keywords

  • Adult, Area Under Curve, Diet, Discriminant Analysis, Fasting, Fatty Acids, Female, Gastrointestinal Tract, Glucose, Glucose Tolerance Test, Health, Humans, Least-Squares Analysis, Metabolome, Middle Aged, Obesity, Phenotype, Physical Fitness, Sedentary Behavior, Weight Loss, Xenobiotics
  • Digital Object Identifier (doi)

    Author List

  • Campbell C; Grapov D; Fiehn O; Chandler CJ; Burnett DJ; Souza EC; Casazza GA; Gustafson MB; Keim NL; Newman JW
  • Start Page

  • e84260
  • Volume

  • 9
  • Issue

  • 1