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However, current anti\u2010obesity therapies target appetite regulation or nutrient absorption without directly correcting this local dysfunction. Here, we report a bioinspired organic single\u2010atom nanozyme for localized thermocatalytic reprogramming of obese adipose tissue. The nanomedicine comprises atomically dispersed ruthenium catalytic centers embedded within a polydopamine framework (Ru@PDA), integrating enzyme\u2010mimetic catalytic activity, antioxidant function, and NIR\u2010II photothermal responsiveness into a single biocompatible platform. Delivered via an injectable crosslinked hyaluronic acid hydrogel for sustained retention in subcutaneous WAT, Ru@PDA exhibits superoxide dismutase\u2010 and catalase\u2010like activities, efficiently scavenges reactive oxygen and nitrogen species, alleviates hypoxia, and generates mild hyperthermia to activate thermogenic signaling. These synergistic effects remodel the pathological adipose microenvironment, promoting adipocyte browning, lipolysis, adiponectin secretion, and anti\u2010inflammatory macrophage polarization. In diet\u2010induced obese mice, localized treatment reduced subcutaneous WAT (\u223c66%), distal visceral fat (\u223c68%), and body weight (\u223c16.9%), while largely restoring glycometabolic homeostasis and alleviating systemic oxidative stress and inflammation. Collectively, this work establishes thermo\u2010catalytic reprogramming of the pathological adipose microenvironment as a promising therapeutic strategy for obesity and related metabolic disorders.<\/jats:p>","DOI":"10.1002\/adhm.71832","type":"journal-article","created":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:40:59Z","timestamp":1791970859000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["A Bioinspired Nanomedicine for Thermo\u2010Catalytic Reprogramming of Obese Fat"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5626-5752","authenticated-orcid":false,"given":"Ehsan","family":"Zolfaghari","sequence":"first","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melisa Wei Ning","family":"Leoi","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lewen","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lynette Xiang","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2268-5050","authenticated-orcid":false,"given":"Zheye","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aung","family":"Than","sequence":"additional","affiliation":[{"name":"School of Chemistry Chemical Engineering and Biotechnology Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2837-5889","authenticated-orcid":false,"given":"Melvin Khee Shing","family":"Leow","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Tan Tock Seng Hospital  Singapore"},{"name":"Lee Kong Chian School of Medicine Institute for Digital Molecular Analytics and Science Nanyang Technological University  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asim","family":"Shabbir","sequence":"additional","affiliation":[{"name":"Department of Surgery National University Hospital  Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1283-6334","authenticated-orcid":false,"given":"Dong\u2010Sheng","family":"Li","sequence":"additional","affiliation":[{"name":"College of Materials and Chemical Engineering Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials China Three Gorges University Yichang P. 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