The natural compound rutaecarpine promotes white adipocyte browning through activation of the AMPK-PRDM16 axis
The natural compound rutaecarpine promotes white adipocyte browning through activation of the AMPK-PRDM16 axis
复制标题
天然化合物芸香碱通过激活 AMPK-PRDM16 轴促进白色脂肪细胞褐变。
DOI：
10.1016/j.bbrc.2021.01.080
复制
发表时间：
2021-02-06
影响因子：
3.1
通讯作者：
Wu, Donghai
中科院分区：
文献类型：
--
作者：
Liu, Xiaomin;Zhang, Yuwei;Wu, Donghai
肥胖症的流行率在全球范围内不断增加，并与许多代谢紊乱有关，如2型糖尿病和心血管疾病。近年来，许多研究表明，促进白色脂肪布朗宁代表了对抗肥胖及其相关代谢紊乱的有希望的策略。本研究的目的是鉴定诱导脂肪细胞布朗宁的化合物并阐明其作用机制。在筛选的500种天然化合物中，一种名为吴茱萸次碱的小分子被鉴定为脂肪细胞布朗宁的体外和体内正调节剂。RNA-seq数据的KEGG通路分析表明，AMPK信号通路受到吴茱萸次碱的调节，这一点通过Western blot分析得到验证。此外，AMPK信号的抑制减轻了布朗宁的吴茱萸碱的效果。当AMPK通路的下游靶点Prdm 16缺失时，吴茱萸次碱对脂肪细胞布朗宁的影响也被消除。吴茱萸次碱是一种诱导脂肪细胞布朗宁的有效化学物质，有可能成为治疗肥胖症的潜在药物。(c)2021爱思唯尔公司All rights reserved.
The prevalence of obesity is increasing globally and is associated with many metabolic disorders, such as type 2 diabetes and cardiovascular diseases. In recent years, a number of studies suggest that promotion of white adipose browning represents a promising strategy to combat obesity and its related metabolic disorders. The aim of this study was to identify compounds that induce adipocyte browning and elucidate their mechanism of action. Among the 500 natural compounds screened, a small molecule named Rutaecarpine, was identified as a positive regulator of adipocyte browning both in vitro and in vivo. KEGG pathway analysis from RNA-seq data suggested that the AMPK signaling pathway was regulated by Rutaecarpine, which was validated by Western blot analysis. Furthermore, inhibition of AMPK signaling mitigated the browning effect of Rutaecaripine. The effect of Rutaecaripine on adipocyte browning was also abolished upon deletion of Prdm16, a downstream target of AMPK pathway. In collusion, Rutaecarpine is a potent chemical agent to induce adipocyte browning and may serve as a potential drug candidate to treat obesity.(c) 2021 Elsevier Inc. All rights reserved.