Wu-Mei-Wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of HSF1

Abstract Background 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...

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Main Authors: Shen Chen, Kexin Nie, Hongzhan Wang, Yang Gao, Xinyue Jiang, Hao Su, Zhi Wang, Yueheng Tang, Fuer Lu, Hui Dong, Jingbin Li
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Chinese Medicine
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Online Access:https://doi.org/10.1186/s13020-024-01053-2
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author Shen Chen
Kexin Nie
Hongzhan Wang
Yang Gao
Xinyue Jiang
Hao Su
Zhi Wang
Yueheng Tang
Fuer Lu
Hui Dong
Jingbin Li
author_facet Shen Chen
Kexin Nie
Hongzhan Wang
Yang Gao
Xinyue Jiang
Hao Su
Zhi Wang
Yueheng Tang
Fuer Lu
Hui Dong
Jingbin Li
author_sort Shen Chen
collection DOAJ
description Abstract Background 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. Methods 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. Results 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. Conclusions WMW represents a potent therapeutic strategy for obesity, promoting metabolic health and beneficial modulation of adipose tissue through an HSF1-dependent pathway.
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spelling doaj-art-0bfae0e5f2bb44e68d0f7261de230bb92025-01-05T12:46:05ZengBMCChinese Medicine1749-85462025-01-0120112210.1186/s13020-024-01053-2Wu-Mei-Wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of HSF1Shen Chen0Kexin Nie1Hongzhan Wang2Yang Gao3Xinyue Jiang4Hao Su5Zhi Wang6Yueheng Tang7Fuer Lu8Hui Dong9Jingbin Li10Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyInstitute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyAbstract Background 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. Methods 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. Results 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. Conclusions WMW represents a potent therapeutic strategy for obesity, promoting metabolic health and beneficial modulation of adipose tissue through an HSF1-dependent pathway.https://doi.org/10.1186/s13020-024-01053-2Wu-Mei-WanObesityHeat shock factor 1White adipose tissueBrown adipose tissue
spellingShingle Shen Chen
Kexin Nie
Hongzhan Wang
Yang Gao
Xinyue Jiang
Hao Su
Zhi Wang
Yueheng Tang
Fuer Lu
Hui Dong
Jingbin Li
Wu-Mei-Wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of HSF1
Chinese Medicine
Wu-Mei-Wan
Obesity
Heat shock factor 1
White adipose tissue
Brown adipose tissue
title Wu-Mei-Wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of HSF1
title_full Wu-Mei-Wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of HSF1
title_fullStr Wu-Mei-Wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of HSF1
title_full_unstemmed Wu-Mei-Wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of HSF1
title_short Wu-Mei-Wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of HSF1
title_sort wu mei wan enhances brown adipose tissue function and white adipose browning in obese mice via upregulation of hsf1
topic Wu-Mei-Wan
Obesity
Heat shock factor 1
White adipose tissue
Brown adipose tissue
url https://doi.org/10.1186/s13020-024-01053-2
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