Localized delivery and retention of hydrogen sulfide causing regional lipid accumulation in mouse adipose tissues in...

Therapeutical application of hydrogen sulfide (H₂S) is limited due to the lack of delivery routes for specific organs and the rapid and wide dispersal of H₂S in vivo. While H₂S shows adipogenic effects in vitro, its in vivo impacts on obesity remain unclear. This study applies a H₂S-slow-releasing hydrogel (H₂S gel) to deliver H₂S locally in subcutaneous adipose tissue and examines local lipid accumulation in mice. H₂S is released from H₂S gels within 6 h and lasts for 72 h, elevating H₂S levels in local adipose tissue but not in the plasma. Localized H₂S 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-γ, adiponectin, and perilipin are all upregulated by H₂S gel injections. Local delivery and retention of H₂S in adipose tissues increase lipid accumulation more in wild-type than in cystathionine-γ-lyase knockout mice. This study confirms the feasibility of selectively delivering H₂S via injectable hydrogels and their effectiveness in regulating targeted tissue functions. Furthermore, this work deepens our understanding of the role of H₂S in obesity development under physiological conditions and offers a practical implementation strategy for H₂S-based therapeutic interventions.