Celastrol targets CKB-mediated futile creatine cycle in human brown adipocytes thermogenesis.

ABSTRACT: Celastrol is widely recognized as one of the most potent anti-obesity agents, and its ability to promote adipocyte thermogenesis is thought to be a key mechanism. However, the precise molecular targets through which celastrol modulates thermogenesis in human adipocytes remain unclear. In this study, we synthesized a celastrol-based small molecular probe and employed a combination of photoaffinity labeling (PAL), click chemistry, and Surface Plasmon Resonance (SPR) to identify its direct binding targets. Our results reveal that celastrol directly interacts with creatine kinase B-type (CKB), leading to an increase in CKB protein stability. This suggests that celastrol modulates the futile creatine cycle within human brown adipocytes, thereby contributing to thermogenesis. Collectively, our f

SUBMITTER: Ni J 

PROVIDER: S-EPMC11984619 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature