{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:48:21Z","timestamp":1793908101359,"version":"4.8.0"},"reference-count":120,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Gouty arthritis (GA) is driven by NLRP3 inflammasome activation, yet its underlying metabolic mechanisms remain poorly explored. Current therapies focus on uric acid reduction and anti-inflammation, often overlooking the plasticity of macrophages controlled by metabolic reprogramming. This review systematically dissects the metabolic shifts in GA, particularly the transition from oxidative phosphorylation (OXPHOS) to glycolysis (Warburg effect) and the unique role of lipid\/amino acid metabolism. We describe macrophage immunometabolism, tricarboxylic acid (TCA)cycle breakpoints, and metabolite functions, with particular emphasis on the \u201cmetabolic-epigenetic\u201d axis (e.g., lactate conversion). We summarize emerging nanotherapeutic strategies (e.g., nanoenzymes, biomimetic carriers) precisely targeting these metabolic checkpoints. Current reviews on GA primarily focus on conventional anti-inflammatory and uric acid-lowering strategies. However, although macrophages are central drivers of the GA disease process, the mechanisms underlying the coupling of their metabolic reprogramming and polarization have not yet been fully elucidated. In particular, metabolite-mediated \u201cmetabolic-epigenetic\u201d crosstalk, as well as how to precisely regulate these metabolic targets using emerging nanotargeting technologies, remain blind spots in current research. This paper is the first to systematically integrate these dimensions, aiming to fill this gap by exploring novel nanostrategies and future prospects for treating GA through the remodeling of macrophage immunometabolism. Targeting macrophage metabolism offers a paradigm shift for GA\u2014from conventional symptom management to targeted disease resolution by directly inhibiting glycolytic flux and succinate accumulation, thereby repolarizing pro-inflammatory M1 macrophages into the tissue-repairing M2 phenotype.<\/jats:p>","DOI":"10.3389\/fphar.2026.1794487","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:54:09Z","timestamp":1777442049000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Rewiring macrophage immunometabolism in gouty arthritis: from metabolic checkpoints to intelligent nano-delivery"],"prefix":"10.3389","volume":"17","author":[{"given":"Feng","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Orthopedics, Shaoyang Hospital of Traditional Chinese Medicine","place":["Shaoyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Shaoyang Hospital of Traditional Chinese Medicine","place":["Shaoyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Shaoyang Hospital of Traditional Chinese Medicine","place":["Shaoyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Shaoyang Hospital of Traditional Chinese Medicine","place":["Shaoyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qixiang","family":"Qin","sequence":"additional","affiliation":[{"name":"The First Clinical Medical College of Heilongjiang University of Chinese Medicine","place":["Harbin City, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Yongzhou Hospital of Traditional Chinese Medicine","place":["Yongzhou, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Lu","sequence":"additional","affiliation":[{"name":"Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Xiong","sequence":"additional","affiliation":[{"name":"Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Longhui County Hospital of Traditional Chinese Medicine","place":["Shaoyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Xiangtan Hospital of Traditional Chinese Medicine","place":["Xiangtan, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aitian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Shaoyang Hospital of Traditional Chinese Medicine","place":["Shaoyang, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Orthopedics, Shaoyang Hospital of Traditional Chinese Medicine","place":["Shaoyang, Hunan, China"]},{"name":"Hunan University of Chinese Medicine","place":["Changsha, Hunan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.4078\/jrd.2024.0054","article-title":"The pathogenesis of gout","volume":"32","author":"Ahn","year":"2025","journal-title":"J. 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