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

National Science Review 2023年第1期10卷 127-142页

作者： Xu Wang Keke Xing Mengge He Ting He Xinkuan Xiang Tao Chen Luoying Zhang Haohong Li Britton Chance Center for Biomedical Photonics Wuhan National Laboratory for OptoelectronicsHuazhong University of Science and Technology MOE Key Laboratory for Biomedical Photonics Collaborative 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

High-fat diet(HFD)-induced obesity is a growing epidemic and major health *** 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 *** paraventricular thalamic nucleus(PVT) plays a role in maintaining *** found that chronic HFD impaired the activity of PVT ***,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 *** the other hand,enhancing PVT neuronal activity cons olidated wakefulness in mice with HFD-induced *** observed that the fragmented wakefulness could be eliminated and reversed by ***,TRF prevented the HFD-induced disruptions on synaptic transmission in the PVT,in a feeding duration-dependent ***,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 *** establish a link between TRF and neural activity,through which TRF can potentially serve as a lifestyle intervention against diet/obesity-related ED S.

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

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time-restricted feeding downregulates cholesterol biosynthesis program via RORγ-mediated chromatin modification in porcine liver organoids

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Journal of Animal Science and Biotechnology 2021年第1期12卷 402-414页

作者： Kexin Zhang Hao Li Zimeng Xin Yanwei Li Xiaolong Wang Yun Hu Haoyu Liu Demin Cai College of Animal Science and Technology Yangzhou UniversityYangzhou 225009PR China Institute of Epigenetics and Epigenomics Yangzhou UniversityYangzhou 225009PR China

Background: time-restricted feeding(TRF) is a dieting strategy based on nutrients availability and diurnal rhythm,shown to improve lipid metabolism efficiency. We have demonstrated previously that retinoic acid-related(RAR)orphan receptor(ROR) γ is the primary transcription factor controlling cholesterol(CHO) biosynthesis program of animals. However, the functional role of RORγ in liver physiology of pigs in response to TRF has not been determined, largely due to the lack of functional models and molecular tools. In the present study, we established porcine liver organoids and subjected them to restricted nutrients supply for 10-h during the light portion of the ***: Our results showed that TRF regimen did not alter hepatocyte physiology, including unchanged cell viability, caspase 3/7 enzyme activity and the gene signature of cell proliferation in porcine liver organoids,compared to the control group(P > 0.05). Furthermore, we found that TRF downregulated the hepatic CHO biosynthesis program at both mRNA and protein levels, along with the reduced cellular CHO content in porcine liver organoids(P < 0.05). Using unbiased bioinformatic analysis of a previous ChIP-seq data and ChIP-qPCR validation, we revealed RORγ as the predominant transcription factor that responded to TRF, amongst the 12 targeted nuclear receptors(NRs)(P < 0.05). This was likely through RORγ direct binding to the MVK gene(encoding mevalonate kinase). Finally, we showed that RORγ agonists and overexpression enhanced the enrichment of cofactor p300, histone marks H3 K27 ac and H3K4me1/2, as well as RNA polymerase II(Pol-II) at the locus of MVK, in TRF-porcine liver organoids, compared to TRF-vector control(P < 0.05).Conclusions: Our findings demonstrate that TRF triggers the RORγ-mediated chromatin remodeling at the locus of CHO biosynthesis genes in porcine liver organoids and further improves lipid metabolism.

关键词： Cholesterol biosynthesis program Histone modification Pig Porcine liver organoids RORγ time-restricted feeding

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time-restricted feeding:what we have done and what more we can do?

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Hepatobiliary Surgery and Nutrition 2023年第3期12卷 440-442页

作者： Yuning Sun Yuqian Ye Yuqin He Shaoyan Liu Department of Head&Neck Surgical Oncology Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina National Cancer Center/National Clinical Research Center for Cancer BeijingChina

Obesity and other metabolic syndromes such as hypertension,type 2 diabetes,and hyperlipidemia remain a major public health burden *** from higher incidence of cardiovascular diseases,obesity and other abnormal metabolic status also promote cancer development and poor prognosis of cancer patients(1-3).In addition to using different surgical modalities(4),weight management through lifestyle changes has proven to be a more economical and low-risk *** obese patients,whether daily caloric intake can be reasonably restricted is recognized as an important strategy for solving their *** the past few years,intermittent fasting(IF),especially time-restricted feeding(TRF),has shown good clinical weight loss effect(>5%loss from baseline)(5).Moreover,people who participate in IF or TRF can often show good compliance,because compared with traditional dieting,IF or TRF does not require participants to record the specific calories of each meal in detail,participants only need to eat within the specified time period and not have any caloric intake at any other time.

关键词： time-restricted feeding metabolic syndrome circadian rhythm

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Impaired function of the suprachiasmatic nucleus rescues the loss of body temperature homeostasis caused by time-restricted feeding

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Science Bulletin 2020年第15期65卷 1268-1280,M0003,M0004页

作者： Zhihui Zhang Qiaocheng Zhai Yue Gu Tao Zhang Zhengyun Huang Zhiwei Liu Yi Liu Ying Xu Model Animal Research Center Nanjing UniversityNanjing 210061China Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda Genomic Resource Center Soochow UniversitySuzhou 215123China Department of Physiology University of Texas Southwestern Medical CenterDallasTX 75390USA State Key Laboratory of Radiation Medicine and Protection Soochow UniversitySuzhou 215123China

The suprachiasmatic nucleus(SCN)is the master circadian pacemaker that drives body temperature ***-restricted feeding(TRF)has potential as a preventative or therapeutic approach against many *** potential side effects of TRF remain *** we show that daily 4-h TRF treatment in mice can severely impair body temperature homeostasis and can result in *** half of the mice died at 21℃,and all mice died at 18℃during 4-h *** effect was modulated by the circadian clock and was associated with severe hypothermia due to loss of body temperature ***,disrupting the circadian clock by SCN lesions or constant light rescued lethality during *** of circadian gene expression in the dorsomedial hypothalamus(DMH)demonstrated that TRF reprograms rhythmic transcriptome in DMH and suppresses expression of genes,such as Ccr5 and Calcrl,which are involved in ***,our results demonstrated a potent effect of TRF on body temperature homeostasis and the role of SCN function in this *** results further suggested that circadian arrhythmicity can have potential beneficial effects under certain stress conditions.

关键词： time-restricted feeding Body temperature Hypothermia Circadian clock The suprachiasmatic nucleus The dorsomedial hypothalamus

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