title: Improved metabolic health alters host metabolism in parallel with changes in systemic xeno-metabolites of gut origin.
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.
authors.affiliation: USDA-ARS Western Human Nutrition Research Center, Davis, California, United States of America.
authors.forename: Caitlin
authors.initials: C
authors.lastname: Campbell
authors.affiliation: West Coast Metabolomics Center, University of California Davis, Davis, California, United States of America.
authors.forename: Dmitry
authors.initials: D
authors.lastname: Grapov
authors.affiliation: 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.
authors.forename: Oliver
authors.initials: O
authors.lastname: Fiehn
authors.affiliation: USDA-ARS Western Human Nutrition Research Center, Davis, California, United States of America.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Chandler
authors.affiliation: USDA-ARS Western Human Nutrition Research Center, Davis, California, United States of America.
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Burnett
authors.affiliation: USDA-ARS Western Human Nutrition Research Center, Davis, California, United States of America.
authors.forename: Elaine C
authors.initials: EC
authors.lastname: Souza
authors.affiliation: Sports Medicine Program, University of California, Davis School of Medicine, Sacramento, California, United States of America.
authors.forename: Gretchen A
authors.initials: GA
authors.lastname: Casazza
authors.affiliation: USDA-ARS Western Human Nutrition Research Center, Davis, California, United States of America.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Gustafson
authors.affiliation: 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.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Keim
authors.affiliation: 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.
authors.forename: John W
authors.initials: JW
authors.lastname: Newman
authors.affiliation: 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.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hunter
authors.affiliation: Department of Nutrition Sciences, University of Alabama, Birmingham, Alabama, United States of America.
authors.forename: Jose R
authors.initials: JR
authors.lastname: Fernandez
authors.affiliation: Department of Nutrition Sciences, University of Alabama, Birmingham, Alabama, United States of America.
authors.forename: W Timothy
authors.initials: WT
authors.lastname: Garvey
authors.affiliation: Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Harper
authors.affiliation: Pharmacology Department, Case Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Hoppel
authors.affiliation: Genome Center, University of California Davis, Davis, California, United States of America.
authors.forename: John K
authors.initials: JK
authors.lastname: Meissen
authors.affiliation: Genome Center, University of California Davis, Davis, California, United States of America.
authors.forename: Kohei
authors.initials: K
authors.lastname: Take
authors.affiliation: 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.
authors.forename: Sean H
authors.initials: SH
authors.lastname: Adams
mesh_terms: D000328:Adult; D019540:Area Under Curve; D004032:Diet; D016002:Discriminant Analysis; D005215:Fasting / Q000097:blood; D005227:Fatty Acids / Q000097:blood; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D005951:Glucose Tolerance Test; D006262:Health; D006801:Humans; D016018:Least-Squares Analysis; D055442:Metabolome; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000378:metabolism; D010641:Phenotype; D010809:Physical Fitness; D057185:Sedentary Behavior; D015431:Weight Loss; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D005227:Fatty Acids; D015262:Xenobiotics; D005947:Glucose