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PLoS One. 2014 Jan 8;9(1):e84260. doi: 10.1371/journal.pone.0084260. eCollection 2014.

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

Author information

1
USDA-ARS Western Human Nutrition Research Center, Davis, California, United States of America.
2
West Coast Metabolomics Center, University of California Davis, Davis, California, United States of America.
3
West Coast Metabolomics Center, University of California Davis, Davis, California, United States of America ; Genome Center, University of California Davis, Davis, California, United States of America.
4
Sports Medicine Program, University of California, Davis School of Medicine, Sacramento, California, United States of America.
5
USDA-ARS Western Human Nutrition Research Center, Davis, California, United States of America ; Department of Nutrition, University of California Davis, Davis, California, United States of America.
6
Department of Nutrition Sciences, University of Alabama, Birmingham, Alabama, United States of America ; Human Studies Department, University of Alabama, Birmingham, Alabama, United States of America.
7
Department of Nutrition Sciences, University of Alabama, Birmingham, Alabama, United States of America.
8
Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
9
Pharmacology Department, Case Western Reserve University, Cleveland, Ohio, United States of America.
10
Genome Center, University of California Davis, Davis, California, United States of America.

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.

PMID:
24416208
PMCID:
PMC3885560
DOI:
10.1371/journal.pone.0084260
[Indexed for MEDLINE]
Free PMC Article

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