Thermogenic effect of withaferin A predicted via transcriptome profiling of cold-exposed tissues
10.7644/j.issn.1674-9960.2025.08.003
- VernacularTitle:基于冷暴露差异基因表达谱预测的产热化合物醉茄素A活性评价研究
- Author:
Mingjie FENG
1
;
Xiaochang ZHANG
;
Jiangbo LI
;
Chenhui WANG
;
Wei HAN
;
Xiaoen GENG
;
Zhe ZHOU
Author Information
1. 军事科学院军事医学研究院,北京 100850
- Keywords:
cold exposure;
mice;
drug repurposing;
adipose tissue thermogenesis;
withaferin A
- From:
Military Medical Sciences
2025;49(8):576-581
- CountryChina
- Language:Chinese
-
Abstract:
Objective To identify candidate compounds that activate thermogenesis during cold exposure by integrating the Library of Integrated Network-Based Cellular Signatures(LINCS)with RNA expression profiles specific to cold-induced thermogenesis.Methods Gene expression profiles of interscapular brown adipose tissue(BAT)and inguinal white adipose tissue(iWAT)were generated from 8-week-old C57BL/6J mice which were housed at 5 ℃ or room temperature(23 ℃)for 7 days.The gene expression signatures of the cold-induced BAT and iWAT were compared to the LINCS dataset to predict potential candidates for testing in a cold challenge model that was intended to assess thermogenesis activation.The pharmacological potential of the identified compounds was evaluated in a cold-exposed mouse model.The core body temperature and infrared thermal imaging were collected to monitor physiological responses during cold exposure.Additionally,hematoxylin and eosin(HE)staining was used to assess morphological changes of fat cells of BAT,iWAT,and epididymal white adipose tissue(eWAT).Results The transcriptomic signatures related to cold-induced thermogenesis were obtained and the top 20 candidate compounds were identified by comparison with the LINCS dataset.Mice treated with withaferin A(WA)during the cold challenge exhibited elevated rectal temperatures and smaller adipocyte sizes compared to controls.Conclusion Our drug repurposing strategy,which connects transcriptional profiles with LINCS data,identifies potential compounds.WA enhances thermogenesis and metabolic activity in adipose tissue,which helps maintain body temperature,and improves cold tolerance during exposure to low temperatures.
