Hua Hu, Zhang Yue, Zhao Fei, Chen Ke, Wu Tong, Liu Qianqi, Huang Songming, Zhang Aihua, Jia Zhanjun
Nanjing Key Laboratory of Pediatrics, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, Nanjing 210008, P. R. of China.
Department of Nephrology, Children's Hospital of Nanjing Medical University, Guangzhou Road #72, Nanjing 210008, P. R. of China.
iScience. 2021 Jan 20;24(2):102077. doi: 10.1016/j.isci.2021.102077. eCollection 2021 Feb 19.
Celastrol, a compound extracted from traditional Chinese medicine, has been reported as a potent anti-obesity agent with controversial mechanisms. Here both C57BL/6J and leptin-deficient () mice fed a high-fat diet (HFD) displayed body weight loss after celastrol therapy, opposing the previous viewpoint that celastrol improves obesity by sensitizing leptin signaling. More importantly, celastrol downregulated lipid transporters in the intestine, increased lipid excretion in feces, and reduced body weight gain in HFD mice. Meanwhile, analysis of gut microbiota revealed that celastrol altered the gut microbiota composition in HFD-fed mice, and modulating gut microbiota by antibiotics or fecal microbiota transplantation blocked the celastrol effect on intestinal lipid transport and body weight gain, suggesting a critical role of the gut microbiota composition in mediating the anti-obesity role of celastrol under HFD. Together, the findings revealed that celastrol reduces intestinal lipid absorption to antagonize obesity by resetting the gut microbiota profile under HFD feeding.
雷公藤红素是一种从中药中提取的化合物，据报道它是一种具有争议性作用机制的强效抗肥胖剂。在这里，喂食高脂饮食（HFD）的C57BL/6J小鼠和瘦素缺陷型小鼠在接受雷公藤红素治疗后体重均减轻，这与之前认为雷公藤红素通过增强瘦素信号来改善肥胖的观点相悖。更重要的是，雷公藤红素下调了肠道中的脂质转运蛋白，增加了粪便中的脂质排泄，并减少了HFD小鼠的体重增加。同时，对肠道微生物群的分析表明，雷公藤红素改变了喂食HFD小鼠的肠道微生物群组成，并且通过抗生素或粪便微生物群移植来调节肠道微生物群会阻断雷公藤红素对肠道脂质转运和体重增加的作用，这表明肠道微生物群组成在介导HFD条件下雷公藤红素的抗肥胖作用中起着关键作用。总之，这些发现揭示了雷公藤红素通过在HFD喂养条件下重置肠道微生物群谱来减少肠道脂质吸收，从而对抗肥胖。
