Human metabolic chambers reveal a coordinated metabolic-physiologic response to nutrition.

Publisher: American Society for Clinical Investigation Country of Publication: United States NLM ID: 101676073 Publication Model: Electronic Cited Medium: Internet ISSN: 2379-3708 (Electronic) Linking ISSN: 23793708 NLM ISO Abbreviation: JCI Insight Subsets: MEDLINE

Original Publication: Ann Arbor, Michigan : American Society for Clinical Investigation, [2016]-

Energy Metabolism*/physiology ; Metabolome*; Humans ; Male ; Female ; Adult ; Calorimetry, Indirect ; Oxidation-Reduction ; Middle Aged ; Fasting/metabolism ; Young Adult ; Carnitine/metabolism ; Carnitine/analogs & derivatives

Human studies linking metabolism with organism-wide physiologic function have been challenged by confounding, adherence, and precisionHere, we united physiologic and molecular phenotypes of metabolism during controlled dietary intervention to understand integrated metabolic-physiologic responses to nutrition. In an inpatient study of individuals who underwent serial 24-hour metabolic chamber experiments (indirect calorimetry) and metabolite profiling, we mapped a human metabolome onto substrate oxidation rates and energy expenditure across up to 7 dietary conditions (energy balance, fasting, multiple 200% caloric excess overfeeding of varying fat, protein, and carbohydrate composition). Diets exhibiting greater fat oxidation (e.g., fasting, high-fat) were associated with changes in metabolites within pathways of mitochondrial β-oxidation, ketogenesis, adipose tissue fatty acid liberation, and/or multiple anapleurotic substrates for tricarboxylic acid cycle flux, with inverse associations for diets with greater carbohydrate availability. Changes in each of these metabolite classes were strongly related to 24-hour respiratory quotient (RQ) and substrate oxidation rates (e.g., acylcarnitines related to lower 24-hour RQ and higher 24-hour lipid oxidation), underscoring links between substrate availability, physiology, and metabolism in humans. Physiologic responses to diet determined by gold-standard human metabolic chambers are strongly coordinated with biologically consistent, interconnected metabolic pathways encoded in the metabolome.

Update of: medRxiv. 2024 Apr 10:2024.04.08.24305087. doi: 10.1101/2024.04.08.24305087. (PMID: 38645000)

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U01 DK123013 United States DK NIDDK NIH HHS

Keywords: Amino acid metabolism; Carbohydrate metabolism; Intermediary metabolism; Metabolism

0 (acylcarnitine)
S7UI8SM58A (Carnitine)

Date Created: 20241122 Date Completed: 20241122 Latest Revision: 20241130

20241202

PMC11601946

10.1172/jci.insight.184279

39576013