College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350122, China.
School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China.
J Proteome Res. 2021 Oct 1;20(10):4840-4851. doi: 10.1021/acs.jproteome.1c00513. Epub 2021 Sep 16.
The antiobesity effect of celastrol has been reported in numerous studies, but the underlying mechanism remains unclear. It is widely accepted that gut dysbiosis is closely related to obesity. The potential effect of celastrol on microbiota is worth exploring. In this study, the celastrol-induced weight loss was validated in high-fat diet (HFD)-induced obese mice, with the detection of reported phenotypes including a reduction in food intake, augments in dyslipidemia and glucose metabolism, and adipose thermogenesis. The anti-inflammatory effect of celastrol was also proved based on the alterations in serum cytokines. Antibiotic interference showed that gut microbiota contributes to celastrol-induced weight loss. Several key bacteria were identified using shotgun metagenomic sequencing to display the alterations of the intestinal microbiome in obese mice treated with celastrol. Meanwhile, the fecal and serum metabolic profiles were generated by pseudotargeted metabolomics, and changes in some critical metabolites related to appetite and metabolism were detected. Importantly, we applied in silico bidirectional mediation analysis to identify the precise connections among the alterations in gut microbes, serum metabolome, and host phenotypes induced by celastrol treatment for the first time. Therefore, we concluded that the celastrol-induced microbial changes partially contribute to the antiobesity effect via the serum metabolome. The mass spectrometry data are deposited on MetaboLights (ID: MTBLS3278).
已有大量研究报道了雷公藤红素的抗肥胖作用，但其中的作用机制尚不清楚。人们普遍认为肠道菌群失调与肥胖密切相关，因此雷公藤红素对肠道微生物群的潜在影响值得探索。在这项研究中，验证了雷公藤红素在高脂饮食（HFD）诱导的肥胖小鼠中诱导体重减轻的作用，并检测了包括减少食物摄入、血脂代谢和葡萄糖代谢增强以及脂肪产热增加在内的报告表型。基于血清细胞因子的变化，还证明了雷公藤红素的抗炎作用。抗生素干扰表明肠道微生物群有助于雷公藤红素诱导的体重减轻。通过 shotgun 宏基因组测序鉴定了几种关键细菌，以显示肥胖小鼠经雷公藤红素治疗后肠道微生物组的变化。同时，通过拟靶向代谢组学生成粪便和血清代谢谱，并检测到与食欲和代谢相关的一些关键代谢物的变化。重要的是，我们首次应用双向中介分析来鉴定雷公藤红素处理引起的肠道微生物、血清代谢组和宿主表型变化之间的确切联系。因此，我们得出结论，雷公藤红素诱导的微生物变化部分通过血清代谢组对其抗肥胖作用有贡献。质谱数据已存入代谢组学数据知识库（ID：MTBLS3278）。
