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United States Department of Agriculture

Agricultural Research Service

Research Project: Linking Foods, Behavior and Metabolism to Promote a Healthy Body Weight

Location: Obesity and Metabolism Research

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

Author
item Campbell, Caitlin
item Grapov, Dmitry
item Fiehn, Oliver
item Chandler, Carol
item Burnett, Dustin
item Souza, Elaine
item Casazza, Gretchen
item Gustafson, Mary
item Keim, Nancy
item Newman, John
item Hunter, Gary
item Fernandez, Jose
item W. Timothy, Garvey
item Harper, Mary-ellen
item Hoppel, Charles
item Meissen, John
item Takeuchi, Kohei
item Adams, Sean

Submitted to: PLoS One
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/30/2014
Publication Date: 1/8/2014
Citation: Campbell, C., Grapov, D., Fiehn, O., Chandler, C.J., Burnett, D.J., Souza, E.C., Casazza, G.A., Gustafson, M.B., Keim, N.L., Newman, J.W., Hunter, G.R., Fernandez, J.R., W. Timothy, G., Harper, M., Hoppel, C.L., Meissen, J.K., Takeuchi, K., Adams, S.H. 2014. Improved metabolic health alters host metabolism in parallel with changes in systemic xeno-metabolites of gut origin. PLoS One. 9(1):e84260. DOI: 10.1371/journal.pone.0084260.

Interpretive Summary: 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 '-tocopherol); (2) Increased indices of saturated very long chain fatty acid elongation capacity; (3) Increased post-OGTT alpha-ketoglutaric acid (alpha-KG), fasting alpha-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.

Technical 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 '-tocopherol); (2) Increased indices of saturated very long chain fatty acid elongation capacity; (3) Increased post-OGTT alpha-ketoglutaric acid (alpha-KG), fasting alpha-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.

Last Modified: 8/24/2016
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