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

Chen Suzhen; Liu Xiaoxiao; Peng ChaoTan ChangSun HonglinLiu HeZhang YaoWu PingCui CanLiu ChuchuYang DiLi ZhiqiangLu JunxiGuan JianKe XisongWang RenxiaoBo XiaohaiXu XiaojunHan JunfengLiu Junli

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

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

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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-1 alpha 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.

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《Cell metabolism》 |2021年第3期|565-580|共23页
作者
Chen Suzhen; Liu Xiaoxiao; Peng ChaoTan ChangSun HonglinLiu HeZhang YaoWu PingCui CanLiu ChuchuYang DiLi ZhiqiangLu JunxiGuan JianKe XisongWang RenxiaoBo XiaohaiXu XiaojunHan JunfengLiu Junli;
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Chinese Acad Sci, Shanghai Adv Res Inst, Natl Facil Prot Sci Shanghai, Zhangjiang Lab, Shanghai;

Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Ctr Chem Biol, Shanghai;

Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Endocrinol & Metab, Shanghai Diabet InstQingdao Univ, Affiliated Hosp, Qingdao, Peoples R ChinaShanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Otolaryngol Head & Neck Surg, ShanghaiChinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032Shanghai Normal Univ, Dept Chem, 100 Guilin Rd, Shanghai 200234, Peoples R ChinaChina Pharmaceut Univ, State Key Lab Nat Med, Nanjing 210009, Jiangsu, Peoples R China;

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中图分类内分泌腺疾病及代谢病;
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The phytochemical hyperforin triggers thermogenesis in adipose tissue via a Dlat-AMPK signaling axis to curb obesity

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