{"doi":"10.1016/j.jbc.2022.102418","title":"Multi-OMICs analysis reveals metabolic and epigenetic changes associated with macrophage polarization","abstract":"Macrophages (M) are an essential immune cell for defense and repair that travel to different tissues and adapt based on local stimuli. A critical factor that may govern their polarization is the crosstalk between metabolism and epigenetics. However, simultaneous measurements of metabolites, epigenetics, and proteins (phenotype) have been a major technical challenge. To address this, we have developed a novel triomics approach using mass spectrometry to comprehensively analyze metabolites, proteins, and histone modifications in a single sample. To demonstrate this technique, we investigated the metabolic-epigenetic-phenotype axis following polarization of human blood-derived monocytes into either 'proinflammatory M1-' or 'anti-inflammatory M2-' Ms. We report here a complex relationship between arginine, tryptophan, glucose, and the citric acid cycle metabolism, protein and histone posttranslational modifications, and human macrophage polarization that was previously not described. Surprisingly, M1-Ms had globally reduced histone acetylation levels but high levels of acetylated amino acids. This suggests acetyl-CoA was diverted, in part, toward acetylated amino acids. Consistent with this, stable isotope tracing of glucose revealed reduced usage of acetyl-CoA for histone acetylation in M1-Ms. Furthermore, isotope tracing also revealed Ms uncoupled glycolysis from the tricarboxylic acid cycle, as evidenced by poor isotope enrichment of succinate. M2-Ms had high levels of kynurenine and serotonin, which are reported to have immune-suppressive effects. Kynurenine is upstream of de novo NAD + metabolism that is a necessary cofactor for Sirtuin-type histone deacetylases. Taken together, we demonstrate a complex interplay between metabolism and epigenetics that may ultimately influence cell phenotype.","journal":"Journal of Biological Chemistry","year":2022,"id":242113,"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":39,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9571,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":640561,"name":"Hui Tang","orcid":"0000-0002-7274-1487","position":1,"is_corresponding":false},{"id":361040,"name":"Vipul K. Singh","orcid":"0000-0002-7146-7279","position":2,"is_corresponding":false},{"id":361039,"name":"Arshad Khan","orcid":"0000-0003-3655-2854","position":3,"is_corresponding":false},{"id":568884,"name":"Abhishek Mishra","orcid":"0000-0003-2077-0937","position":4,"is_corresponding":false},{"id":297929,"name":"Blanca I. Restrepo","orcid":"0000-0002-3743-9098","position":5,"is_corresponding":false},{"id":857902,"name":"Chinnaswamy Jagannath","orcid":"0000-0002-3014-2857","position":6,"is_corresponding":false},{"id":568883,"name":"Kangling Zhang","orcid":"0000-0003-2151-9218","position":7,"is_corresponding":false},{"id":872355,"name":"Mark L. Sowers","orcid":"0000-0001-6474-017X","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T00:23:05.485568Z","pmid":"36030823","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":[]}