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This review delineates core concepts, key signalling nodes\u2014emphasising the mechanistic target of rapamycin (mTOR) as an integrator of metabolic and immune signals\u2014research and intervention strategies across metabolic and infectious diseases. Immune cells display metabolic plasticity: At rest, they depend mainly on mitochondrial oxidative phosphorylation, but swiftly shift to aerobic glycolysis upon activation to fuel effector functions. Pro\u2010inflammatory subsets like Th1 cells and M1 macrophages lean heavily on glycolysis, whereas regulatory T cells favour fatty acid oxidation. Central pathways\u2014glycolysis, the tricarboxylic acid (TCA) cycle, and amino acid metabolism\u2014directly shape immune activation and inflammation via intermediates and regulatory enzymes. For example, succinate and itaconic acid are critical in inflammation control, while fatty acid and cholesterol metabolism dictate immune cell fate. In metabolic disorders such as obesity, diabetes, fatty liver disease, and atherosclerosis, immune metabolic reprogramming is the main driver of chronic low\u2010grade inflammation and tissue injury. During infection, a metabolic tug\u2010of\u2010war ensues: Pathogens hijack host metabolism for survival, and the host counters by reprogramming its own metabolism. The idea of \u201ctrained immunity\u201d highlights how metabolism\u2013epigenetics crosstalk endows innate immunity with memory\u2010like capacity. These insights inform therapeutic avenues\u2014modulating metabolic pathways, nutritional interventions, and microbiome targeting\u2014with wide potential. Challenges remain, including the complexity of in\u00a0vivo networks and the need for precise interventions. Yet advances in single\u2010cell multi\u2010omics and metabolic flux analysis will deepen mechanistic understanding and enable breakthroughs in precision strategies.<\/jats:p>","DOI":"10.1111\/sji.70141","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T06:43:51Z","timestamp":1786949031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Evolution and Mechanistic Insights of Immunometabolism in Metabolic Diseases and Infections"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3157-6819","authenticated-orcid":false,"given":"Wenbin","family":"Tan","sequence":"first","affiliation":[{"name":"Jining Medical University  Jining Shandong Province 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