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Protein & Cell 2023年第4期14卷 309-313页

作者： Xiaolin Liu Yue Ma Ying Yu Wenhui Zhang ingjing Shi Xuan Zhang Min Dai Yuhan Wang Hao Zhang Jiahe Zhang Jianghua Shen Faming Zhang Moshi Song Jun Wang CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China UniversityofChineseAcademyof Sciences Beijing100049China Medical Center for Digestive Diseases the Second Affliated Hospital of Nanjing Medical UniversityNanjing 210011China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing100101China Institute for Stem cell and Regeneration Chinese Academy of SciencesBeijing100101China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China Key Lab of Holistic Integrative Enterology Nanjing Medical University.Nanjing 210011China

Dear Editor,circadian rhythms are the periodic turmover of biological behaviors and physiological functions of many organisms(Allada and Bass,2021).In mammals,circadian rhythms are maintained by the clock system,involving central clock in suprachiasmatic nucleus and peripheral clock in organs like intestine;and at cellular level a cell-autonomous transcriptional and translational feedback loop involving clock genes like BMAL1(brain and muscle ARNT-Like 1,also known as ARNTL),CLOCK(clock circadian regulator),PER1/2/3(period circadian regulator 1/2/3)and CRY1/2(cryptochrome circadian regulator 1/2)(Allada and Bass,2021).

关键词： organs intestine circadian

Endogenous ceramide phosphoethanolamine modulates circadian rhythm via neural-glial coupling in Drosophila

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National Science Review 2022年第12期9卷 104-123页

作者： Xiupeng Chen Jie Li Zhongbao Gao Yang Yang Wenqing Kuang Yue Dong Gek Huey Chua Xiahe Huang Binhua Jiang He Tian Yingchun Wang Xun Huang Yan Li Sin Man Lam Guanghou Shui State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences University of Chinese Academy of Sciences State Key Laboratory of Brain and Cognitive Science Institute of Biophysics Chinese Academy of Sciences Lipid ALL Technologies Company Limited

While endogenous lipids are known to exhibit rhythmic oscillations,less is known about how specific lipids modulate circadian behavior.Through a series of loss-of-function and gain-of-function experiments on cer amide phosphoethanolamine(CPE) synthase of Drosophila,we demonstrated that pan-glial-specific deficiency in membrane CPE,the structural analog of mammalian sphingomyelin(SM),leads to arrhythmic locomotor behavior and shortens lifespan,while the reverse is true for increasing CPE.Comparative proteomics uncovered dysregulated synaptic glutamate utilization and transport in CPE-deficient flies.An extensive genetic screen was conducted to verify the role of differentially expressed proteins in circadian regulation.Arrhythmic locomotion under cpes1mutant background was rescued only by restoring endogenous CPE or SM through expressing their respective synthases.Our results underscore the essential role of CPE in maintaining synaptic glutamate homeostasis and modulating circadian behavior in Drosophila.The findings suggest that region-specific elevations of functional membrane lipids can benefit circadian regulation.

关键词： ceramide phosphoethanolamine sphingomyelin circadian longevity glutamate homeostasis

circadian rhythms in the pathogenesis of gastrointestinal diseases

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World Journal of Gastroenterology 2018年第38期24卷 4297-4303页

作者： Pilar Codonr-Franch Marie Gombert Department of Pediatrics Obstetrics and GinecologyUniversity of ValenciaValencia 46010Spain Department of Pediatrics Dr.Peset University HospitalValencia 46017Spain Department of Biotechnology University of La RochelleLa Rochelle 17000France

The etiology of digestive pathologies such as irritable bowel syndrome(IBS), inflammatory bowel diseases(IBD) and cancer is not yet fully understood. In recent years, several studies have evidenced circadian variations in mechanisms involved in digestive health. In situations of disturbed circadian rhythms(chronodisruption) where the central clock and the peripheral clocks receive incoherent signals, the synchronicity is lost producing implications for health. This lack of coordination could alter the tissue function and cause long term damage to the organs. Life habits such as sleep, physical exercise, social interaction, and feeding times are determinants for stability and integrity of circadian rhythms. In recent years, experimental and clinical studies have consistently evidenced that the alteration of circadian rhythms is associated with the development of digestive pathologies mainly linked to dismotility or changes in microbiota composition. Likewise, it seems reasonable to deep into the importance of chronodisruption as a factor that may participate in the development of pathologies such as IBS, IBD and digestive cancers. Moreover, life habits respecting circadian rhythms should be promoted for the prevention of these diseases. Further studies will allow us a better understanding of the mechanisms acting at molecular level, and the development of new therapeutic targets.

关键词： circadian rhythms Gastrointestinal diseases Irritable bowel syndrome Inflammatory bowel disease Digestive cancers

circadian rhythms of hormone secretion and obesity

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World Journal of Diabetes 2018年第11期9卷 195-198页

作者： Rajendra Raghow Department of Veterans Affairs Medical Center MemphisTN 38104United States Department of Pharmacology University of Tennessee Health Science CenterMemphisTN 38163United States

The adipose tissue homeostasis is profoundly affected by circadian rhythms of corticosteroid secretion and chronic loss of hormonal oscillations is associated with obesity. How adipose tissue differentially responds to pulsatile vs continuous presence of glucocorticoids is poorly defined. To address this question, Bahrami-Nejad et al studied differentiation of pre-adipocytes, containing endogenously tagged CCAAT/enhancer binding protein and peroxisome proliferator-activated receptor(PPAR) γ(key regulators of adipocyte differentiation), in response to corticosteroids that were delivered either in an oscillatory fashion or continuously. The authors show that the bi-stable state of differentiation of pre-adipocytes and adipocytes was regulated by a combination of fast and slow positive feedback networks, that determined unique threshold of PPARγ in these cells. Evidently, pre-adipocytes used the fast feedback loop to reject differentiation cues of oscillating pulses of glucocorticoids and failed to differentiate into fat cells. In contrast, when glucocorticoids were delivered continuously, precursor cells exploited the slow feedback loop to embark on a path of maximal differentiation. This differential differentiation response of pre-adipocytes to pulsatile vs continuous exposure to glucocorticoids was corroborated in vivo. Thus, mice receiving non-oscillating doses of exogenous glucocorticoids, for 21 d, elicited excessive accumulation of visceral and subcutaneous fat. These data shed new light on the mechanisms of obesity caused by putative misalignment of circadian secretion of glucocorticoids or their persistently high levels due to chronic stress or Cushing's disease.

关键词： circadian rhythms Glucocorticoids Adipose tissue Pre-adipocytes Stem cells Terminal differentiation

Extent of mismatch between the period of circadian clocks and light/dark cycles determines time-to-emergence in fruit flies

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Insect Science 2015年第4期22卷 569-577页

作者： Pankaj Yadav Deepak Choudhury Madhumala K. Sadanandappa Vijay Kumar Sharma Chronobiology Laboratory Evolutionary and Organismal Biology Unit Jawaharlal Nehru Centre for Advanced Scientific Research Bangalore 560064 Kamataka India

circadian clocks time developmental stages of fruit flies Drosophila melanogaster, while light/dark （LD） cycles delimit emergence of adults, conceding only during the ＂allowed gate.＂ Previous studies have revealed that time-to-emergence can be altered by mutations in the core clock gene period （per）, or by altering the length of LD cycles. Since this evidence came from studies on genetically manipulated flies, or on flies maintained under LD cycles with limited range of periods, inferences that can be drawn are limited. Moreover, the extent of shortening or lengthening of time-to-emergence re- mains yet unknown. In order to pursue this further, we assayed time-to-emergence of D. rnelanogaster under 12 different LD cycles as well as in constant light （LL） and constant dark conditions （DD）. Time-to-emergence in flies occurred earlier under LL than in LD cycles and DD. Among the LD cycles, time-to-emergence occurred earlier under T4-T8, followed by T36-T48, and then T12-T32, suggesting that egg-to-emergence duration in flies becomes shorter when the length of LD cycles deviates from 24 h, bearing a strong positive and a marginally negative correlation with day length, for values shorter and longer than 24 h, respectively. These results suggest that the extent of mismatch between the period of circadian clocks and environmental cycles determines the time-to-emergence in Drosophila.

关键词： circadian Drosophila light/dark regimes period time-to-emergence

Diurnal Regulation of Lipid Metabolism and Applications of circadian Lipidomics

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Journal of Genetics and Genomics 2014年第5期41卷 231-250页

作者： Joshua J.Gooley Eric Chern-Pin Chua Program in Neuroscience and Behavioral Disorders Duke-NUS Graduate Medical SchoolSingapore Division of Sleep and circadian Disorders Departments of Medicine and Neurology Brigham and Women's Hospital Division of Sleep Medicine Harvard Medical School Program in Neuroscience and Behavioral Disorders Duke-NUS Graduate Medical School Singapore

The circadian timing system plays a key role in orchestrating lipid metabolism. In concert with the solar cycle, the circadian system ensures that daily rhythms in lipid absorption, storage, and transport are temporally coordinated with rest-activity and feeding cycles. At the cellular level, genes involved in lipid synthesis and fatty acid oxidation are rhythmically activated and repressed by core clock proteins in a tissue-specific manner. Consequently, loss of clock gene function or misalignment of circadian rhythms with feeding cycles （e.g., in shift work） results in impaired lipid homeostasis. Herein, we review recent progress in circadian rhythms research using lipidomics, i.e., large-scale profiling of lipid metabolites, to characterize circadian-regulated lipid pathways in mammals. In mice, novel regulatory circuits involved in fatty acid metabolism have been identified in adipose tissue, liver, and muscle. Extensive diversity in circadian regulation of plasma lipids has also been revealed in humans using lipidomics and other metabolomics approaches. In future studies, lipidomics platforms will be increasingly used to better understand the effects of genetic variation, shift work, food intake, and drugs on circadian-regulated lipid pathways and metabolic health.

关键词： circadian Metabolism Lipids Lipidomics Metabolomics Chronobiology

Gut microbiota:closely tied to the regulation of circadian clock in the development of type 2 diabetes mellitus

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Chinese Medical Journal 2020年第7期133卷 817-825页

作者： Lu Ding Xin-Hua Xiao Department of Endocrinology Key Laboratory of EndocrinologyMinistry of HealthPeking Union Medical College HospitalDiabetes Research Center of Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Type 2 diabetes mellitus(T2DM),a worldwide epidemic disease,has caused tremendous economic and social burden,but the pathogenesis remains uncertain.Nowadays,the impact of unrhythmic circadian clock caused by irregular sleep and unhealthy diet on T2DM has be increasingly studied.However,the contribution of the endogenous circadian clock system to the development of T2DM has not yet been satisfactorily explored.It is now becoming clear that the gut microbiota and the circadian clock interact with each other to regulate the host metabolism.Considering all these above,we reviewed the literature related to the gut microbiota,circadian clock,and T2DM to elucidate the idea that the gut microbiota is closely tied to the regulation of the circadian clock in the development of T2DM,which provides potential for gut microbiota-directed therapies to ameliorate the effects of circadian disruptions linked to the occurrence and development of T2DM.

关键词： Gut microbiota circadian clock Type 2 diabetes mellitus Metabolites

Time for a Nuclear Meeting： Protein Trafficking and Chromatin Dynamics Intersect in the Plant circadian System

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Molecular Plant 2012年第3期5卷 554-565页

作者： Eva Herrero Seth J. Davis Max Planck Institute for Plant Breeding Research Carl-von-Linne＇weg 10 50829 Cologne Germany Present address： MRC National Institute for Medical Research The Ridgeway Mill Hill NW7 1AA London UK

circadian clocks mediate adaptation to the 24-h world. In Arabidopsis, most circadian-clock components act in the nucleus as transcriptional regulators and generate rhythmic oscillations of transcript accumulation. In this review, we focus on post-transcriptional events that modulate the activity of circadian-clock components, such as phosphorylation, ubiquitination and proteasome-mediated degradation, changes in cellular localization, and protein-protein interactions. These processes have been found to be essential for circadian function, not only in plants, but also in other circadian systems. Moreover, light and clock signaling networks are highly interconnected. In the nucleus, light and clock compo- nents work together to generate transcriptional rhythms, leading to a general control of the timing of plant physiological processes.

关键词： circadian light signaling chromatin cellular dynamics ubiquitin/proteasome-mediated proteolysis

β-Arrestin 1(ARRB1) serves as a molecular marker of the peripheral circadian rhythm

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International Journal of Oral Science 2019年第4期11卷 307-314页

作者： Tatsunosuke Tomita Taisuke Mori Yoshiaki Onishi Biomedical Research Institute National Institute of Advanced Industrial Science and Technology(AIST)DBT-AIST International Laboratory for Advanced Biomedicine(DAILAB)Higashi 1-1-1TsukubaJapan Molecular Pathology Division and Diagnostic Pathology Division National Cancer Center Research InstituteTsukiji 5-5-1Chuo-kuTokyoJapan

The control of the circadian rhythm is important for health because it regulates physiological functions and is associated with health hazards.We aimed to identify a circadian biomarker of health status in human saliva,since collecting saliva is non-invasive,straightforward,and cost-effective.Among 500 genes potentially controlled by the salivary clock identified using chromatin immunoprecipitation(ChIP)assays,22 of them showed reasonable transcriptional responses according to a DNA array in a salivary model system.Among these 22 genes,ARRB1,which is expressed in human salivary glands,was also expressed in model HSG cells at the transcriptional and translational levels.The profile of ARRB1 expression in human saliva was circadian,suggesting that ARRB1 could serve as a candidate circadian biomarker in saliva.We compared ARRB1 with other biomarkers in salivary samples from jetlagged individuals.The circadian profile of ARRB1 reflected the time lag more than the profile of melatonin,whereas the profiles of cortisol andα-amylase did not reflect the time lag.Overall,these findings suggest that salivary ARRB1 could serve as a candidate biomarker that could be used to monitor the internal body clock.

关键词： salivary circadian straight

Carcinogenic efects of circadian disruption: an epigenetic viewpoint

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Chinese Journal of Cancer 2015年第9期34卷 1-9页

作者： Abbas Salavaty Department of Genetics Faculty of ScienceShahid Chamran University of Ahvaz

circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, afects many biological processes within the body and results in diferent long-term diseases, including cancer. circadian regulatory pathways result in rhythmic epigenetic modiications and the formation of circadian epigenomes. Aberrant epigenetic modiications, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic efects of circadian disruption. In this review, I irst discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modiications that result in circadian disruption. In addition, I explain the carcinogenic efects of circadian disruption and highlight its potential role in diferent human cancers using an epigenetic viewpoint. Finally, the importance of chronotherapy in cancer treatment is highlighted.

关键词： Cancer, Epigenetics, circadian rhythms, circadian disruption, Chronotherapy