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In this pathogenic process, the dysregulated interaction between adipocytes and adipose-resident immune cells plays a critical regulatory role; however, the underlying mechanisms governing this abnormal interaction remain largely unknown. In this study, we showed that upregulated \u03b22-microglobulin expression in hypertrophic adipocytes during obesity not only mediated the activation of adipose-resident CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells in a cell contact-dependent manner but also facilitated iron overload and the ferroptosis of adipocytes, thereby promoting the M1 polarization of adipose tissue macrophages. Conversely, specific ablation of \u03b22-microglobulin in adipocytes effectively suppressed the activation and accumulation of adipose-resident CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, as well as adipocyte ferroptosis and M1 polarization, ultimately preventing high-fat diet-induced obesity and its related inflammation and metabolic disorders. Additionally, adeno-associated virus-mediated adipose-targeted knockdown of \u03b22-microglobulin has been demonstrated to therapeutically alleviate high-fat diet-induced obesity, as well as its related chronic inflammation and metabolic disorders. Furthermore, our bioinformatic analysis of human adipose transcriptome data revealed a strong correlation between adipose \u03b22-microglobulin and obesity. More importantly, \u03b22-microglobulin is significantly upregulated in adipocytes isolated from patients with obesity. Thus, our findings highlight the pivotal role of adipocytes in obesity-associated chronic inflammation and metabolic disorders via \u03b22-microglobulin-dependent mechanisms.\n                  <\/jats:p>","DOI":"10.1038\/s41392-025-02486-3","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:02:50Z","timestamp":1764720170000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Adipocytes orchestrate obesity-related chronic inflammation through \u03b22-microglobulin"],"prefix":"10.1038","volume":"10","author":[{"given":"Jie","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shushu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengjie","family":"Duan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meiling","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengjun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4959-0729","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuzhang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"2486_CR1","doi-asserted-by":"publisher","first-page":"972","DOI":"10.1016\/S0140-6736(24)01210-8","volume":"404","author":"I Lingvay","year":"2024","unstructured":"Lingvay, I. & Cohen, R. 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