Akebia Saponin D Targeting Ubiquitin Carboxyl-Terminal Hydrolase 4 Promotes Peroxisome Proliferator-Activated Receptor Gamma Deubiquitination and Activation of Brown Adipose Tissue Thermogenesis in Obesity.

ABSTRACT: Promoting thermogenesis in adipose tissue to enhance energy expenditure is widely regarded as a promising strategy for obesity treatment. However, the development of effective thermogenic drugs remains challenging. Our screenings identified the natural compound Akebia Saponin D (ASD) as a potent brown fat thermogenesis activator in mice, showing effects through mitochondrial brown fat uncoupling protein 1 (UCP1)-dependent pathways. ASD was found to significantly mitigate high-fat diet-induced obesity and enhance the mitochondrial quality of brown adipocytes to promote thermogenesis. Utilizing human protein microarrays, cellular thermal shift assay, and drug affinity responsive target stability, along with microscale thermophoresis and molecular docking analysis, we identified ubiquitin car

SUBMITTER: Chen L 

PROVIDER: S-EPMC12521790 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature