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ARS Home » Pacific West Area » Davis, California » Western Human Nutrition Research Center » Obesity and Metabolism Research » Research » Publications at this Location » Publication #295783

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

Author
item CAMPBELL, CAITLIN - UNIVERSITY OF CALIFORNIA
item GRAPOV, DMITRY - UNIVERSITY OF CALIFORNIA
item FIEHN, OLIVER - UNIVERSITY OF CALIFORNIA
item CHANDLER, CAROL - UNIVERSITY OF CALIFORNIA
item BURNETT, DUSTIN - UNIVERSITY OF CALIFORNIA
item SOUZA, ELAINE - UNIVERSITY OF CALIFORNIA
item CASAZZA, GRETCHEN - UNIVERSITY OF CALIFORNIA
item GUSTAFSON, MARY - UNIVERSITY OF CALIFORNIA
item Keim, Nancy
item Newman, John
item HUNTER, GARY - UNIVERSITY OF ALABAMA
item FERNANDEZ, JOSE - UNIVERSITY OF ALABAMA
item W. TIMOTHY, GARVEY - UNIVERSITY OF ALABAMA
item HARPER, MARY-ELLEN - UNIVERSITY OF OTTAWA
item HOPPEL, CHARLES - CASE WESTERN RESERVE UNIVERSITY (CWRU)
item MEISSEN, JOHN - UNIVERSITY OF CALIFORNIA
item TAKEUCHI, KOHEI - UNIVERSITY OF CALIFORNIA
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.