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Macrophages accumulate extensively in RA synovium, and their abundance and functional phenotypes are correlated with disease activity and severity. Disturbed macrophage polarization is a key feature of RA progression, characterized by an increased proportion of classically activated (M1) macrophages and a reduced proportion of alternatively activated (M2) macrophages. M1 macrophages produce proinflammatory mediators that sustain synovial inflammation and contribute to progressive joint damage. Accumulating evidence indicates that immune cell functions are closely linked to metabolic programs. The synovial microenvironment in RA is marked by hypoxia, acidosis, and nutrient limitation, which lead to substantial metabolic reprogramming during macrophage polarization. Importantly, metabolic changes occur not merely secondary to polarization but actively shape the phenotypic transition of macrophages. In this review, we summarize the current evidence on how dysregulation of glucose, lipid, and amino acid metabolism regulates the phenotype switching of macrophages in RA. We discuss the roles of key metabolic enzymes and intermediates in macrophage polarization, consider the diagnostic potential of metabolic biomarkers, and highlight therapeutic opportunities targeting metabolic pathways, thereby resolving macrophage imbalance and improving RA outcomes.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70253-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1002\/art.70253","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T08:55:52Z","timestamp":1781772952000},"page":"2203-2220","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Metabolic Dysregulation on Macrophage Polarization in Rheumatoid Arthritis"],"prefix":"10.1002","volume":"78","author":[{"given":"Xinyue","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences Peking Union Medical College  Beijing China"},{"name":"National Clinical Research Center for Dermatologic and Immunologic Diseases (NCRC\u2010DID) Ministry of Science &amp; 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