{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T07:25:51Z","timestamp":1787124351120,"version":"build-2736575974"},"reference-count":229,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273997"],"award-info":[{"award-number":["82273997"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82322002"],"award-info":[{"award-number":["82322002"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Macrophages orchestrate immune responses through remarkable phenotypic plasticity, which is intrinsically linked to their ability to reprogram intracellular metabolic pathways in response to microenvironmental cues. While recent advances have highlighted the role of aberrant macrophage metabolism in diverse diseases, a systematic synthesis integrating both intracellular and extracellular metabolic signals remains lacking. This review provides a comprehensive framework for understanding\u00a0how core metabolic pathways\u2014glycolysis, the TCA cycle, oxidative phosphorylation (OXPHOS), fatty acid oxidation (FAO), and amino acid metabolism\u2014are rewired during macrophage polarization under the orchestration of upstream signaling cascades, including NF\u2010\u03baB, PI3K\/AKT\/mTOR, JAK\u2013STAT, and MAPK. We examine how exogenous metabolites such as succinate, itaconate, lactate, and amino acids reciprocally regulate macrophage function and discuss tissue\u2010specific metabolic signatures of macrophage subsets\u2014including alveolar macrophages \uff08AMs), Kupffer cells (KCs), and tumor\u2010associated macrophages (TAMs)\u2014in the context of obesity, Type 2 diabetes (T2D), metabolic dysfunction\u2010associated steatotic liver disease (MASLD), infections, autoimmune disorders, and cancer. We further evaluate emerging therapeutic strategies targeting macrophage metabolism, summarizing preclinical and clinical advances across signaling pathways, metabolic nodes, cytokines, and cell\u2010based therapies with detailed trial data. By integrating cell\u2010intrinsic metabolic circuitry with extracellular signals, this review establishes a theoretical foundation for metabolism\u2010targeted immunotherapies and identifies key knowledge gaps for future investigation.<\/jats:p>","DOI":"10.1002\/mco2.70868","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T06:48:51Z","timestamp":1784789331000},"source":"Crossref","is-referenced-by-count":0,"title":["Metabolic Regulation of Macrophages in Health and Disease"],"prefix":"10.1002","volume":"7","author":[{"given":"Shan","family":"Huang","sequence":"first","affiliation":[{"name":"National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology, and Department of Metabolism and Endocrinology Ministry of Education The Second Xiangya Hospital of Central South University  Changsha Hunan 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Department of Metabolism and Endocrinology Ministry of Education The Second Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Li","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology, and Department of Metabolism and Endocrinology Ministry of Education The Second Xiangya Hospital of Central South University  Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"National Clinical Research Center for Metabolic Diseases Key Laboratory of Diabetes Immunology, and Department of Metabolism and Endocrinology Ministry of Education The Second Xiangya Hospital of Central South University  Changsha Hunan 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