Celastrol prevents high-fat diet-induced obesity by promoting white adipose tissue browning.
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ABSTRACT:
SUBMITTER: Wang B
PROVIDER: S-EPMC8673360 | biostudies-literature | 2021 Dec
REPOSITORIES: biostudies-literature
Publications
Celastrol prevents high-fat diet-induced obesity by promoting white adipose tissue browning.
Wang Bingwei B Yang Xiaoning X Zhao Miao M Su Zhijie Z Hu Zhiping Z Zhang Chenyu C Guo Bingbing B Liu Jiarui J Qin Lihua L Zhang Weiguang W Zheng Ruimao R
Clinical and translational medicine 20211201 12
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Project description:Background/objectivesMounting evidence indicates that the short-chain fatty acid butyrate protects against obesity and associated comorbidities, partially through the induction of adipose tissue thermogenesis. However, the effects of butyrate on white adipose tissue (WAT) browning and its molecular mechanism are still elusive. The objective of this study was to investigate butyrate-induced thermogenesis in white adipose tissue and its underlying mechanism.MethodsWe studied the effects of butyrate on diet-induced obesity in the humanized APOE*3-Leiden.CETP transgenic mouse model and explored factors related to white adipose browning. Specifically, mice were challenged with a high-fat diet supplemented with butyrate. Adiposity was measured to assess obesity development. Energy metabolism was detected using an indirect calorimetry system. RNA-seq analysis was conducted to analyze the transcription landscape of WAT and responsible targets. Furthermore, the revealed molecular mechanism was verified in vitro.ResultsButyrate alleviated high-fat diet-induced obesity and promoted energy expenditure accompanied by brown adipose tissue activation and WAT browning. Mechanistically, RNA-seq analysis revealed that butyrate downregulated HDAC9 in WAT. Additionally, butyrate decreased HDAC9 while increasing thermogenesis in vitro. Inhibition of HDAC9 with TMP269 promoted thermogenic gene expression, mimicking the effects of butyrate.ConclusionsButyrate protects against diet-induced obesity accompanied by decreasing the expression of HDAC9 in white adipose tissue and inducing browning. This study reveals a new mechanism whereby butyrate activates adaptive thermogenesis and provides new insights for the development of weight-loss drugs targeting adipose HDAC9.
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