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Mitochondrial dysfunction and oxidative stress are closely implicated in the pathogenesis of obesity. Therefore, targeting adipose mitochondrial function to reduce mitochondrial reactive oxygen (mROS) levels can enhance mitochondrial activity and promote thermogenesis, presenting a promising therapeutic strategy for obesity. In this study, we developed cationic liposomes (AE@PEP\u2010Lip) specifically designed for adipose mitochondrial targeting. These liposomes can effectively accumulate in white adipose tissue due to their highly positively charged surface, and subsequently localize to mitochondria via the mitochondrial\u2010targeting peptide SS\u201031. The SS\u201031 peptide efficiently scavenges mROS and synergizes with empagliflozin in AE@PEP\u2010Lip to inhibit mitochondrial fragmentation, thereby enhancing mitochondrial respiration and thermogenic capacity. Furthermore, allicin, which is loaded into AE@PEP\u2010Lip and released into the cytoplasm, activates the AMPK signaling pathway and upregulates uncoupling proteins, further promoting mitochondrial thermogenesis. In obese mice, treatment with AE@PEP\u2010Lip improved mitochondrial morphology and function and induced browning characteristics. Moreover, we demonstrated the clinical application potential of AE@PEP\u2010Lip in reducing localized fat deposition using a porcine model. Taken together, this study presents a novel and promising therapeutic platform for obesity by modulating adipose mitochondrial function.<\/jats:p>","DOI":"10.1002\/adhm.202505925","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T07:14:37Z","timestamp":1775891677000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mitochondria\u2010Targeted Liposomes Boost Thermogenesis for Adipose Tissue Regulation"],"prefix":"10.1002","volume":"15","author":[{"given":"Shibo","family":"Tian","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine Sichuan Agricultural University  Chengdu Sichuan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailong","family":"Xie","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Sichuan Agricultural University  Chengdu Sichuan 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