Identification of an alternative ligand-binding pocket in peroxisome proliferator-activated receptor gamma and its correlated selective agonist for promoting beige adipocyte differentiation.

ABSTRACT: The pharmacological activation of peroxisome proliferator-activated receptor gamma (PPARγ) is a convenient and promising strategy for promoting beige adipocyte biogenesis to combat obesity-related metabolic disorders. However, thiazolidinediones (TZDs), the full agonists of PPARγ exhibit severe side effects in animal models and in clinical settings. Therefore, the development of efficient and safe PPARγ modulators for the treatment of metabolic diseases is emerging. In this study, using comprehensive methods, we report a previously unidentified ligand-binding pocket (LBP) in PPARγ and link it to beige adipocyte differentiation. Further virtual screening of 4097 natural compounds based on this novel LBP revealed that saikosaponin A (NJT-2), a terpenoid compound, can bind to PPARγ to induce

SUBMITTER: Tian Q 

PROVIDER: S-EPMC11233932 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature