Celastrol alleviates metabolic disturbance in high‐fat diet‐induced obese mice through increasing energy expenditure by ameliorating metabolic inflammation

• DOI: 10.1002/ptr.6800
• Publication Date: 2020-08-10T07:41:41Z
• Authors: Xueping Yang; Fan Wu; Lingli Li; Ernest C. Lynch; Linglin Xie; Yan Zhao; Ke Fang; Jingbin Li; Jinlong Luo; Lijun Xu; Xin Zou; Fuer Lu; Guang Chen
• Keywords: Inflammation; Male; 0301 basic medicine; 2. Zero hunger; Inflammasomes; Macrophages; Anti-Inflammatory Agents; Mice, Obese; Diet, High-Fat; 3. Good health; Mice, Inbred C57BL; Mice; 03 medical and health sciences; Adipose Tissue; Liver; Glucose Intolerance; Animals; Cytokines; Anti-Obesity Agents; Obesity; Insulin Resistance; Energy Metabolism; Pentacyclic Triterpenes; Dyslipidemias

Celastrol, a natural triterpene, has been shown to treat obesity and its related metabolic disorders. In this study, we first assessed the relationship between the antiobesity effects of celastrol and its antiinflammatory activities. Our results showed that celastrol can reduce weight gain, ameliorate glucose intolerance, insulin resistance, and dyslipidemia without affecting food intake in high‐fat diet‐induced obese mice. A CLAMS was used to clarify the improvement of metabolic profiles was attribute to increased adipose thermogenesis after celastrol treatment. Further studies found that celastrol decreased the infiltration of macrophage as well as its inflammatory products (IL‐1β, IL‐18, MCP‐1α, and TNF‐α) in liver and adipose tissues, which also displayed an obvious inhibition of TLR3/NLRP3 inflammasome molecules. This study demonstrated that celastrol could be a potential drug for treating metabolic disorders, the underlying mechanism is related to ameliorating metabolic inflammation, thus increasing body energy expenditure.