Increasing evidence indicates that disturbance of the clock genes,which leads to systemic endocrine perturbation,plays a crucial role in the pathogenesis of metabolic and liver diseases.Fluorene-9-bisphenol(BHPF)is ut...Increasing evidence indicates that disturbance of the clock genes,which leads to systemic endocrine perturbation,plays a crucial role in the pathogenesis of metabolic and liver diseases.Fluorene-9-bisphenol(BHPF)is utilized in the manufacturing of plastic materials but its biological effects on liver homeostasis remain unknown.The impacts and involved mechanisms of BHPF on the liver diseases,metabolism,and circadian clock were comprehensively studied by zebrafish andmouse models.The therapeutic effect of melatonin(MT)was also verified.Zebrafish and mousemodels with either acute exposure(0.5 and 1μmol/L,1-4 days post-fertilization)or chronic oral exposure(0.5 and 50 mg/(kg·2 days),30 days)were established with various BHPF concentrations.Herein,we identified a crucial role for estrogenic regulation in liver development and circadian locomotor rhythms damaged by BHPF in a zebrafish model.BHPF mice showed chaos in circadian activity through the imbalance of circadian clock component Brain and Muscle Aryl hydrocarbon receptor nuclear translocator-like 1 in the liver and brain.The liver sexual dimorphic alteration alongwith reduced growth hormone and estrogens played a critical role in damaged glucose metabolism,hepatic inflammation,and fibrosis induced by BHPF.Besides,sleep improvement by exogenous MT alleviated BHPF-related glucose metabolism and liver injury in mice.We proposed the pathogenesis of metabolic and liver disease resulting from BHPF and promising targeted therapy for livermetabolism disorders associated with endocrine perturbation chemicals.These results might play a warning role in the administration of endocrine-disrupting chemicals in everyday life and various industry applications.展开更多
基金supported by the National Natural Science Foundation of China(No.62027812)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJSYXZDXK006)Tianjin Municipal Bureau of Public Health(No.RC20037).
文摘Increasing evidence indicates that disturbance of the clock genes,which leads to systemic endocrine perturbation,plays a crucial role in the pathogenesis of metabolic and liver diseases.Fluorene-9-bisphenol(BHPF)is utilized in the manufacturing of plastic materials but its biological effects on liver homeostasis remain unknown.The impacts and involved mechanisms of BHPF on the liver diseases,metabolism,and circadian clock were comprehensively studied by zebrafish andmouse models.The therapeutic effect of melatonin(MT)was also verified.Zebrafish and mousemodels with either acute exposure(0.5 and 1μmol/L,1-4 days post-fertilization)or chronic oral exposure(0.5 and 50 mg/(kg·2 days),30 days)were established with various BHPF concentrations.Herein,we identified a crucial role for estrogenic regulation in liver development and circadian locomotor rhythms damaged by BHPF in a zebrafish model.BHPF mice showed chaos in circadian activity through the imbalance of circadian clock component Brain and Muscle Aryl hydrocarbon receptor nuclear translocator-like 1 in the liver and brain.The liver sexual dimorphic alteration alongwith reduced growth hormone and estrogens played a critical role in damaged glucose metabolism,hepatic inflammation,and fibrosis induced by BHPF.Besides,sleep improvement by exogenous MT alleviated BHPF-related glucose metabolism and liver injury in mice.We proposed the pathogenesis of metabolic and liver disease resulting from BHPF and promising targeted therapy for livermetabolism disorders associated with endocrine perturbation chemicals.These results might play a warning role in the administration of endocrine-disrupting chemicals in everyday life and various industry applications.
