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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 Unit

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

Authors
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: November 13, 2013
Publication Date: January 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: 9/20/2014
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