{"doi":"10.1101/2023.12.06.570456","title":"Individual dietary amino acid restrictions induce distinct metabolic and chromatin states","abstract":"Abstract Dietary protein and essential amino acid (EAA) restriction promote favorable metabolic reprogramming, although the extent to which shared or EAA-specific mechanisms facilitate diet-associated phenotypes remains unclear. Here, we compared the physiological and molecular effects of dietary methionine, leucine, or isoleucine depletion (Met-D, Leu-D, and Ile-D) in C57BL/6J mice. Each diet elicited responses not phenocopied by mTORC1 inhibition, including reduced fat mass and hepatic amino acid catabolism. Ile-D yielded additional distinct responses, highlighted by histone H2A/H4 hypoacetylation and maintained hepatic acetyl-CoA levels despite downregulated FA β-oxidation. Multi-Omics Factor Analysis of 14,139 data points objectively affirmed Ile-D phenotypes are distinct from Met-D or Leu-D and identified several metabolic and chromatin features as primary discriminators. Metabolic and epigenetic responses to Ile-D were recapitulated in vitro , suggesting underlying mechanisms represent fundamental cellular properties. Together, these results demonstrate EAAs can stimulate unique phenotypes and highlight distinct molecular mechanisms by which EAAs may inform metabolic health.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":393908,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1168402,"name":"Yang Liu","orcid":"0000-0002-2422-2922","position":1,"is_corresponding":false},{"id":430391,"name":"Cara L. Green","orcid":"0000-0002-2293-9364","position":2,"is_corresponding":false},{"id":848559,"name":"Krittisak Chaiyakul","orcid":"0000-0001-8797-880X","position":3,"is_corresponding":false},{"id":1168695,"name":"Pragyan Mishra","orcid":null,"position":4,"is_corresponding":false},{"id":681865,"name":"Reji Babygirija","orcid":"0000-0003-3719-5991","position":5,"is_corresponding":false},{"id":1168696,"name":"Eric A. Armstrong","orcid":null,"position":6,"is_corresponding":false},{"id":1168697,"name":"Anusha T. Mehendale","orcid":null,"position":7,"is_corresponding":false},{"id":298238,"name":"Irene M. Ong","orcid":"0000-0002-9353-6941","position":8,"is_corresponding":false},{"id":285810,"name":"Dudley W. Lamming","orcid":"0000-0002-0079-4467","position":9,"is_corresponding":false},{"id":281307,"name":"John M. Denu","orcid":"0000-0001-9415-0365","position":10,"is_corresponding":false},{"id":281305,"name":"Spencer A. Haws","orcid":"0000-0002-2166-1858","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T01:19:10.334330Z","pmid":"38106163","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":[]}