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

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

doi:10.1093/nsr/nwac222

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

Natl Sci Rev. 2022 Oct 16;10(1):nwac222. doi: 10.1093/nsr/nwac222. eCollection 2023 Jan.

Authors

Xu Wang^{1

2}, Keke Xing³, Mengge He^{1

2}, Ting He^{1

2}, Xinkuan Xiang^{1

2}, Tao Chen³, Luoying Zhang⁴, Haohong Li^{5

6}

Affiliations

¹ Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074, China.
² MOE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan 430074, China.
³ Department of Anatomy, Histology & Embryology, Fourth Military Medical University, Xi'an 710032, China.
⁴ Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
⁵ Department of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
⁶ Liangzhu Laboratory, The MOE Frontier Research Center of Brain & Brain-machine Integration, State Key Laboratory of Brain-machine Intelligence, Hangzhou 311121, China.

Abstract

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 consolidated 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 EDS.

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