Procyanidin B2 (PB2), a phenolic compound existing in berry fruits, grape seed and apple peel, is reportedly to exert multiple health-promoting effects. However, the effect of PB2 on metabolic syndrome and its molecular mechanism remain largely unknown. In the present study, we established free fatty acids (FFAs)-induced cell model and high-fat diet (HFD)-induced mice model to investigate the effect of PB2 on fat accumulation and oxidative stress. Our results indicated that PB2 provided protection against fat accumulation and its associated oxidative stress by inhibiting excessive ROS and superoxide anion radicals, blocking loss of mitochondrial membrane potential and restoring glutathione content in FFAs-induced cell model. Mechanistically, PB2 facilitated lipid degradation by promoting transcription factor EB (TFEB) nuclear translocation, which is a master regulator of lysosomal function. In silico molecular docking study suggested a possible binding position of PB2 with TFEB. Moreover, PB2 contributed to the amelioration of metabolic disorders including obesity and hyperglycemia in HFD-induced obese mice. It was confirmed that PB2 prevented HFD-induced fat accumulation by inhibiting lipogenesis-related gene expression (PPARγ, C/EBPα and SREBP-1c), reducing pro-inflammatory cytokines levels (IL-6 and TNF-α) and increasing antioxidant enzymes activity (GPx, SOD and CAT). In consistent with in vitro results, PB2 restored TFEB protein expression and upregulated TFEB target genes involved in the lysosomal pathway (Lamp1, Mcoln and Uvrag) in HFD-induced mice. Collectively, our results demonstrated that PB2 attenuated metabolic syndrome through activation of TFEB-mediated lysosomal pathway and restoration of redox status, which suggested a previously unrecognized molecular mechanism of PB2 on ameliorating HFD-induced metabolic disorders. This study implicates a potential nutrition intervention strategy for metabolic syndrome by modulation of TFEB pathway, and PB2 could be a novel agent for the prevention and treatment of metabolic syndrome.

Procyanidin B2 attenuates metabolic syndrome by promoting TFEB nuclear translocation and restoring redox status

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.