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Article Publish Status: FREE
Abstract Title:

The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity.

Abstract Source:

Cell Metab. 2021 Mar 2 ;33(3):565-580.e7. PMID: 33657393

Abstract Author(s):

Suzhen Chen, Xiaoxiao Liu, Chao Peng, Chang Tan, Honglin Sun, He Liu, Yao Zhang, Ping Wu, Can Cui, Chuchu Liu, Di Yang, Zhiqiang Li, Junxi Lu, Jian Guan, Xisong Ke, Renxiao Wang, Xiaohai Bo, Xiaojun Xu, Junfeng Han, Junli Liu

Article Affiliation:

Suzhen Chen

Abstract:

Stimulation of adipose tissue thermogenesis is regarded as a promising avenue in the treatment of obesity. However, pharmacologic engagement of this process has proven difficult. Using the Connectivity Map (CMap) approach, we identified the phytochemical hyperforin (HPF) as an anti-obesity agent. We found that HPF efficiently promoted thermogenesis by stimulating AMPK and PGC-1α via a Ucp1-dependent pathway. Using LiP-SMap (limited proteolysis-mass spectrometry) combined with a microscale thermophoresis assay and molecular docking analysis, we confirmed dihydrolipoamide S-acetyltransferase (Dlat) as a direct molecular target of HPF. Ablation of Dlat significantly attenuated HPF-mediated adipose tissue browning both in vitro and in vivo. Furthermore, genome-wide association study analysis indicated that a variation in DLAT is significantly associated with obesity in humans. These findings suggest that HPF is a promising lead compound in the pursuit of a pharmacological approach to promote energy expenditure in the treatment of obesity.

Study Type : Animal Study

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