Time-restricted feeding is an intervention against excessive dark-phase sleepiness induced by obesogenic diet

作     者：Xu Wang Keke Xing Mengge He Ting He Xinkuan Xiang Tao Chen Luoying Zhang Haohong Li Xu Wang;Keke Xing;Mengge He;Ting He;Xinkuan Xiang;Tao Chen;Luoying Zhang;Haohong Li

作者机构：Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and Technology MOE Key Laboratory for Biomedical PhotonicsCollaborative Innovation Center for Biomedical Engineering School of Engineering SciencesHuazhong University of Science and Technology Department of Anatomy Histology &Embryology Fourth Military Medical University Key Laboratory of Molecular Biophysics of Ministry of Education College of Life Science and Technology Huazhong University of Science and Technology Department of Neurobiology Affiliated Mental Health Center &Hangzhou Seventh People's HospitalZhejiang University School of Medicine Liangzhu Laboratory The MOE Frontier Research Center of Brain &Brain-machine Integration State Key Laboratory of Brain-machine Intelligence 

出 版 物：《National Science Review》 (国家科学评论(英文版))

年 卷 期：2023年第10卷第1期

页      面：127-142页

核心收录：

学科分类：1002[医学-临床医学] 10[医学] 

基　　金：supported by the Scientific and Technological Innovation 2030 Program of China (2021ZD0203003) 

主　　题：high-fat diet excessive daytime sleepiness sleep–wake cycle fragmented wakefulness paraventricular thalamic nucleus time-restricted feeding 

摘      要：High-fat diet(HFD)-induced obesity is a growing epidemic and major health concern.While excessive daytime sleepiness(EDS) is a common symptom of HFD-induced obesity,preliminary findings suggest that reduced wakefulness could be improved with time-restricted feeding(TRF).At present,however,the underlying neural mechanisms remain largely unknown.The paraventricular thalamic nucleus(PVT) plays a role in maintaining wakefulness.We found that chronic HFD impaired the activity of PVT neurons.Notably,inactivation of the PVT was sufficient to reduce and fragment wakefulness during the active phase in lean mice,similar to the sleep-wake alterations observed in obese mice with HFD-induced obesity.On the other hand,enhancing PVT neuronal activity cons olidated wakefulness in mice with HFD-induced obesity.We observed that the fragmented wakefulness could be eliminated and reversed by TRF.Furthermore,TRF prevented the HFD-induced disruptions on synaptic transmission in the PVT,in a feeding duration-dependent manner.Collectively,our findings demonstrate that ad libitum access to a HFD results in inactivation of the PVT,which is critical to impaired nocturnal wakefulness and increased sleep,while TRF can prevent and reverse diet-induced PVT dysfunction and excessive sleepiness.We establish a link between TRF and neural activity,through which TRF can potentially serve as a lifestyle intervention against diet/obesity-related ED S.