摘要Background:Long-term exposure to light has emerged as a novel risk factor for metabolic diseases.The whitening of brown adipose tissue(BAT)may play an important role in metabolic disorders caused by long-term continuous light exposure.This study aimed to investigate the morphological and functional alterations in BAT under continuous light conditions and to identify traditional Chinese medicine compounds capable of reversing these changes.Methods:A metabolic disorder model was established by subjecting mice to continuous light exposure for 5 weeks.During this period,body weight,food intake,and body fat percentage were monitored.Serum levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDL-C)were measured to assess lipid metabolism.Histological changes in BAT were examined using H&E staining.The expression of the thermogenic marker uncoupling protein 1(UCP1)in BAT was determined by RT-qPCR and Western blot to evaluate thermogenic function.RNA sequencing(RNA-seq)was employed to identify differentially expressed genes(DEGs)involved in BAT whitening induced by prolonged continuous light exposure.DEGs were analyzed using the connectivity map(CMap)database to identify potential preventive and therapeutic compounds.The therapeutic efficacy of the selected compounds was subsequently evaluated using the above indicators,and key pathways were validated through western blot analysis.Results:After 5 weeks of continuous light exposure,mice exhibited increased body fat percentage and serum levels of TG,impaired mitochondrial function,reduced thermogenic capacity,and whitening of BAT.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses indicated that BAT whitening was primarily associated with the adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,fatty acid metabolism,and circadian rhythm.Ten hub genes identified using Cytoscape were mainly related to AMPK signaling and heat shock proteins.In vivo experiments showed that cordycepin significantly attenuated the increase in body fat percentage caused by prolonged light exposure.This effect was mediated by activation of the AMPK/PGC-1α/UCP1 signaling pathway,which restored the multilocular morphology and thermogenic function of BAT.Conclusion:Cordycepin mitigates continuous light-induced BAT whitening and metabolic disturbances by activating the AMPK signaling pathway.