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While H<jats:sub>2<\/jats:sub>S shows adipogenic effects in vitro, its in vivo impacts on obesity remain unclear. This study applies a H<jats:sub>2<\/jats:sub>S-slow-releasing hydrogel (H<jats:sub>2<\/jats:sub>S gel) to deliver H<jats:sub>2<\/jats:sub>S locally in subcutaneous adipose tissue and examines local lipid accumulation in mice. H<jats:sub>2<\/jats:sub>S is released from H<jats:sub>2<\/jats:sub>S gels within 6\u2009h and lasts for 72\u2009h, elevating H<jats:sub>2<\/jats:sub>S levels in local adipose tissue but not in the plasma. Localized H<jats:sub>2<\/jats:sub>S gel delivery causes significant lipid accumulation and larger lipid droplet diameter in mouse adipose tissues. The expressions of sterol regulatory element-binding protein, peroxisome proliferator-activated receptor-\u03b3, adiponectin, and perilipin are all upregulated by H<jats:sub>2<\/jats:sub>S gel injections. Local delivery and retention of H<jats:sub>2<\/jats:sub>S in adipose tissues increase lipid accumulation more in wild-type than in cystathionine-\u03b3-lyase knockout mice. This study confirms the feasibility of selectively delivering H<jats:sub>2<\/jats:sub>S via injectable hydrogels and their effectiveness in regulating targeted tissue functions. Furthermore, this work deepens our understanding of the role of H<jats:sub>2<\/jats:sub>S in obesity development under physiological conditions and offers a practical implementation strategy for H<jats:sub>2<\/jats:sub>S-based therapeutic interventions.<\/jats:p>","DOI":"10.1038\/s42003-025-08353-9","type":"journal-article","created":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T12:40:47Z","timestamp":1751373647000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Localized delivery and retention of hydrogen sulfide causing regional lipid accumulation in mouse adipose tissues in vivo"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6185-8527","authenticated-orcid":false,"given":"Richa","family":"Verma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hassan M.","family":"Arif","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3575-7786","authenticated-orcid":false,"given":"Guangdong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ishani","family":"Sarkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuljeet","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7984-5396","authenticated-orcid":false,"given":"John B.","family":"Matson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3825-3620","authenticated-orcid":false,"given":"Rui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,1]]},"reference":[{"key":"8353_CR1","doi-asserted-by":"crossref","unstructured":"Abdelaal, M. et al. 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