6‐Gingerol induces browning of white adipose tissue to improve obesity through PI3K/AKT‐RPS6‐mediated thermogenesis pathway
6‐Gingerol induces browning of white adipose tissue to improve obesity through PI3K/AKT‐RPS6‐mediated thermogenesis pathway
复制标题
DOI：
10.1002/fft2.251
复制
发表时间：
2023-05
期刊：
影响因子：
9.9
通讯作者：
Yasmin Alhamoud;Jun-qing Wu;Muhammad Ijaz Ahmad;Fang Chen;Feng-qin Feng-Feng-qin-Feng-35627223;Jing Wang
中科院分区：
文献类型：
--
作者：
Yasmin Alhamoud;Jun-qing Wu;Muhammad Ijaz Ahmad;Fang Chen;Feng-qin Feng-Feng-qin-Feng-35627223;Jing Wang
白色脂肪的布朗宁已经成为一个热门话题，因为它可以帮助减肥和改善代谢健康。因此，本研究旨在探讨生姜中天然活性物质6-姜辣素（6-Gingerol，6 G）的体内布朗宁或生热效应，并阐明其内在机制。结果表明，6 G限制了高脂饮食诱导的肥胖小鼠的体重增加，提高了耐寒性，并增加了能量消耗。此外，组织学和免疫组织化学分析显示，6 G激活棕色脂肪组织（BAT），并在附睾脂肪组织（eWAT）中诱导更多的米色细胞。同时，eWAT布朗宁的标志是多室脂滴的出现，解偶联蛋白1（UCP 1）的水平较高，线粒体含量增加。通过RNA-seq、qPCR和蛋白质印迹测定进一步研究eWAT布朗宁的潜在分子机制。结果表明，6 G显著诱导eWAT中米色和产热特异性标志物的表达，并主要通过磷酸肌醇3-激酶（PI 3 K）/蛋白激酶B（AKT）-核糖体蛋白S6（RPS 6）轴触发产热。一致地，体外数据显示，用PI 3 K/AKT通路抑制剂预处理原代白色脂肪细胞显著抵消了6 G诱导的作用。这项研究首次揭示，6 G通过调节PI 3 K/AKT‐ RPS 6和产热途径诱导脂肪组织的布朗宁，从而缓解肥胖。
The browning of white fat has become a hot topic as it could help to lose weight and improve metabolic health. Therefore, this study aims to explore the in vivo browning or thermogenesis effect of 6‐gingerol (6G), a natural bioactive compound of ginger, and to clarify the underlying mechanism. The results showed that 6G limited weight gain, improved cold tolerance, and increased energy expenditure in high‐fat diet‐induced obese mice. Moreover, histological and immunohistochemical analysis revealed that 6G activated brown adipose tissue (BAT) and induced more beige cells in epididymal adipose tissue (eWAT). Meanwhile, eWAT browning was marked by appearance of multilocular lipid droplets, a higher level of uncoupling protein 1 (UCP1), and increased mitochondrial content. The potential molecular mechanism of eWAT browning was further investigated by RNA‐seq, qPCR, and western blot assays. Results indicated that 6G significantly induced the expression of beige and thermogenesis‐specific markers in eWAT and triggers thermogenesis mainly through a phosphoinositide 3‐kinase (PI3K) / protein kinase B (AKT)‐ribosomal protein S6 (RPS6) axis. Consistently, in vitro, data showed that pretreatment of primary white adipocytes with PI3K/AKT pathway inhibitor significantly counteracted the 6G‐induced effects. This study reveals, for the first time, that 6G induces browning in adipose tissue by modulating the PI3K/AKT‐RPS6 and thermogenesis pathways, thereby alleviating obesity.