1. Improved metabolic health alters host metabolism in parallel with changes in systemic xeno-metabolites of gut origin.
- Author
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Campbell, Caitlin, Grapov, Dmitry, Fiehn, Oliver, Chandler, Carol J, Burnett, Dustin J, Souza, Elaine C, Casazza, Gretchen A, Gustafson, Mary B, Keim, Nancy L, Newman, John W, Hunter, Gary R, Fernandez, Jose R, Garvey, W Timothy, Harper, Mary-Ellen, Hoppel, Charles L, Meissen, John K, Take, Kohei, and Adams, Sean H
- Subjects
Gastrointestinal Tract ,Humans ,Obesity ,Weight Loss ,Glucose ,Fatty Acids ,Xenobiotics ,Glucose Tolerance Test ,Diet ,Fasting ,Area Under Curve ,Discriminant Analysis ,Least-Squares Analysis ,Phenotype ,Physical Fitness ,Adult ,Middle Aged ,Health ,Female ,Metabolome ,Sedentary Behavior ,General Science & Technology - 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
- 2014