Chen Shen, Nie Kexin, Wang Hongzhan, Gao Yang, Jiang Xinyue, Su Hao, Wang Zhi, Tang Yueheng, Lu Fuer, Dong Hui, Li Jingbin
Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Department of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China.
Chin Med. 2025 Jan 3;20(1):1. doi: 10.1186/s13020-024-01053-2.
This research aims to explore the anti-obesity potential of Wu-Mei-Wan (WMW), particularly its effects on adipose tissue regulation in obese mice induced by a high-fat diet (HFD). The study focuses on understanding the role of heat shock factor 1 (HSF1) in mediating these effects.
HFD-induced obese mice were treated with WMW. Body weight, food intake, and histopathological analysis of adipose tissue were conducted. Brown adipose tissue (BAT) activity was evaluated using Positron Emission Tomography, and ultrastructural changes were examined via transmission electron microscopy. Proteomic analysis identified targets of WMW in obesity treatment. HSF1 expression was inhibited to confirm its role. Molecular docking studied interactions between WMW and HSF1. Short-chain fatty acids (SCFAs) in the intestines were measured to determine if WMW's effects on HSF1 are mediated through SCFAs. Protein expression was assessed using western blot, immunohistochemistry, immunofluorescence and RT-qPCR were employed to detect the mRNA levels. Statistical analyses included t-tests, ANOVA, and non-parametric tests like the Mann-Whitney U test or Kruskal-Wallis test.
WMW significantly mitigates the adverse effects of a HFD on body weight and glucose metabolism in obese mice. Both low-dose WMW and high-dose WMW treatments led to reduced weight gain and improved glucose tolerance, with low-dose WMW showing more pronounced effects. WMW also reversed structural damage in BAT, enhancing mitochondrial integrity and thermogenic function, particularly at the low dose. Additionally, WMW treatment promoted the browning of WAT, evidenced by increased expression of key thermogenic proteins such as UCP1 and PGC-1α. The increase in HSF1 expression in both BAT and WAT, observed with WMW treatment, was crucial for these beneficial effects, as inhibition of HSF1 negated the positive outcomes. Furthermore, WMW treatment led to elevated levels of short-chain fatty acids SCFAs in the intestines, which are associated with increased HSF1 expression.
WMW represents a potent therapeutic strategy for obesity, promoting metabolic health and beneficial modulation of adipose tissue through an HSF1-dependent pathway.
本研究旨在探索乌梅丸（WMW）的抗肥胖潜力，尤其是其对高脂饮食（HFD）诱导的肥胖小鼠脂肪组织调节的影响。该研究着重于了解热休克因子1（HSF1）在介导这些作用中的角色。
用WMW处理HFD诱导的肥胖小鼠。进行体重、食物摄入量及脂肪组织的组织病理学分析。使用正电子发射断层扫描评估棕色脂肪组织（BAT）活性，并通过透射电子显微镜检查超微结构变化。蛋白质组学分析确定WMW在肥胖治疗中的靶点。抑制HSF1表达以确认其作用。分子对接研究WMW与HSF1之间的相互作用。测量肠道中的短链脂肪酸（SCFAs），以确定WMW对HSF1的影响是否通过SCFAs介导。使用蛋白质免疫印迹法评估蛋白质表达，采用免疫组织化学、免疫荧光和RT-qPCR检测mRNA水平。统计分析包括t检验、方差分析以及非参数检验，如曼-惠特尼U检验或克鲁斯卡尔-沃利斯检验。
WMW显著减轻HFD对肥胖小鼠体重和葡萄糖代谢的不良影响。低剂量WMW和高剂量WMW处理均导致体重增加减少和葡萄糖耐量改善，低剂量WMW的效果更显著。WMW还逆转了BAT的结构损伤，增强了线粒体完整性和产热功能，尤其是在低剂量时。此外，WMW处理促进了白色脂肪组织（WAT）的棕色化，关键产热蛋白如解偶联蛋白1（UCP1）和过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC-1α）表达增加证明了这一点。WMW处理后在BAT和WAT中观察到的HSF1表达增加对这些有益作用至关重要，因为抑制HSF1会消除积极结果。此外，WMW处理导致肠道中短链脂肪酸SCFAs水平升高，这与HSF1表达增加有关。
WMW是一种有效的肥胖治疗策略，通过依赖HSF1的途径促进代谢健康并对脂肪组织进行有益调节。
