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Although monosodium urate (MSU) crystal deposition remains the central pathognomonic feature, accumulating evidence suggests that free fatty acids (FFAs) play a significant role as co\u2010modulators in the disease's pathogenesis. This review systematically examines the dual role of FFAs in gout pathophysiology: (1) their pro\u2010inflammatory effects during gout flares through direct modulation of innate immune responses, and (2) their role as metabolic modulators contributing to disease comorbidities. We explore the molecular mechanisms by which saturated and n\u20106 polyunsaturated fatty acids (PUFAs) promote NLRP3 inflammasome activation, ultimately leading to cytokine storm formation and acute inflammatory responses. Paradoxically, short\u2010chain fatty acids and n\u20103 polyunsaturated fatty acids exhibit anti\u2010inflammatory properties and confer protection against gout flares via distinct immunomodulatory pathways. The review further examines FFA\u2010mediated metabolic disturbances associated with gout, such as insulin resistance, renal fibrosis, and non\u2010alcoholic fatty liver disease. Additionally, this review provides novel insights into targeted therapeutic strategies for the adjuvant treatment of gout, including lipid\u2010targeted therapy, microbiome modulation, and dietary recommendations regarding polyunsaturated fatty acids.<\/jats:p>","DOI":"10.1111\/1756-185x.70799","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:00:51Z","timestamp":1785412851000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Roles of Free Fatty Acids in Gout Pathogenesis: Inflammatory Drivers and Metabolic Mediators"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3496-2999","authenticated-orcid":false,"given":"Na","family":"Lin","sequence":"first","affiliation":[{"name":"Rheumatology and Immunology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine)  Zhejiang 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