{"doi":"10.17615/ksk6-s229","title":"Human metabolic chambers reveal a coordinated metabolic-physiologic response to nutrition","abstract":"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.","journal":"UNC Libraries","year":2024,"id":506926,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9365,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260540,"name":"Jonathan Krakoff","orcid":"0000-0001-6074-5600","position":1,"is_corresponding":false},{"id":6946,"name":"Clary B. Clish","orcid":"0000-0001-8259-9245","position":2,"is_corresponding":false},{"id":260537,"name":"Paolo Piaggi","orcid":"0000-0003-2774-9161","position":3,"is_corresponding":false},{"id":326584,"name":"Jane E. Freedman","orcid":"0000-0002-0011-6164","position":4,"is_corresponding":false},{"id":801152,"name":"Andrew Perry","orcid":"0000-0003-3342-6158","position":5,"is_corresponding":false},{"id":11361,"name":"Kari E. North","orcid":"0000-0002-8903-0366","position":6,"is_corresponding":false},{"id":236774,"name":"Shi Huang","orcid":"0000-0003-2674-2830","position":7,"is_corresponding":false},{"id":251876,"name":"Ravi V. Shah","orcid":"0000-0002-4471-7156","position":8,"is_corresponding":false},{"id":326582,"name":"Venkatesh L. Murthy","orcid":"0000-0002-7901-1321","position":9,"is_corresponding":false},{"id":255091,"name":"Matthew Nayor","orcid":"0000-0002-6993-9396","position":10,"is_corresponding":false},{"id":16108,"name":"Jennifer E. Below","orcid":"0000-0002-6372-6402","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:10:58.484528Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}