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Myokines:metabolic regulation in obesity and type 2 diabetes

Life Metabolism 2024年第3期3卷 21-45页

作者： Zhi-Tian Chen Zhi-Xuan Weng Jiandie D.Lin zhuo-xian meng Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital School of MedicineZhejiang UniversityHangzhouZhejiang 310058China Key Laboratory of Disease Proteomics of Zhejiang Province School of MedicineZhejiang UniversityHangzhouZhejiang 310058China Zhejiang University-University of Edinburgh Institute(ZJE) School of MedicineZhejiang UniversityHainingZhejiang 314400China Life Sciences Institute and Department of Cell and Developmental Biology University of MichiganAnn ArborMI 48109United States Department of Geriatrics Affiliated Hangzhou First People’s HospitalHangzhouZhejiang 310006China

Skeletal muscle plays a vital role in the regulation of systemic metabolism,partly through its secretion of endocrine factors which are collectively known as *** myokine levels are associated with metabolic diseases,such as type 2 diabetes(T2D).The significance of interorgan crosstalk,particularly through myokines,has emerged as a fundamental aspect of nutrient and energy ***,a comprehensive understanding of myokine biology in the setting of obesity and T2D remains a major chal*** this review,we discuss the regulation and biological functions of key myokines that have been extensively studied during the past two decades,namely interleukin 6(IL-6),irisin,myostatin(MSTN),growth differentiation factor 11(GDF11),fibroblast growth factor 21(FGF21),apelin,brain-derived neurotrophic factor(BDNF),meteorin-like(Metrnl),secreted protein acidic and rich in cysteine(SPARC),β-aminoisobutyric acid(BAIBA),Musclin,and Dickkopf 3(Dkk3).Related to these,we detail the role of exercise in myokine expression and secretion together with their contributions to metabolic physiology and *** significant advancements in myokine research,many myokines remain challenging to measure accurately and investigate ***,new research techniques and detection methods should be developed and rigorously ***,developing a comprehensive perspective on myokine biology is crucial,as this will likely offer new insights into the pathophysiological mechanisms underlying obesity and T2D and may reveal novel targets for therapeutic interventions.

关键词： myokines skeletal muscle obesity type 2 diabetes metabolism

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Transcriptional control of pancreaticβ-cell identity and plasticity during the pathogenesis of type 2 diabetes

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Journal of Genetics and Genomics 2022年第4期49卷 316-328页

作者： Ziyin Zhang Yue Gao zhuo-xian meng Department of Pathology and Pathophysiology and Department of Geriatrics of Affiliated Hangzhou First People’s Hospital Zhejiang University School of MedicineHangzhouChina Key Laboratory of Disease Proteomics of Zhejiang Province Zhejiang University School of MedicineHangzhouZhejiang310058China Department of Geriatrics Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiang310006China

Type 2 diabetes(T2D)is caused by insulin resistance and insufficient insulin *** has increasingly indicated that pancreaticβ-cell dysfunction is the primary determinant of T2D disease progression and *** plasticity is an important feature of pancreaticβ-*** T2D development,pancreaticβ-cells undergo dynamic ***β-cell death/apoptosis in later-stage T2D is the major cause ofβ-cell dysfunction,recent studies have revealed thatβ-cell dedifferentiation and reprogramming,which play critical roles inβ-cell functional regulation in the early and middle T2D progression stages,are characterized by(i)a loss of matureβ-cell-enriched genes;(ii)dedifferentiation to a progenitor-like state;and(iii)transdifferentiation into other cell *** roles of transcription factors(TFs)in the establishment and maintenance ofβ-cell identity during pancreatic development have been extensively ***,we summarize the roles and underlying mechanisms of TFs in the maintenance ofβ-cell identity under physiological and type 2 diabetic *** feasible approaches for restoring islet functions are also discussed.A better understanding of the transcriptional control ofβ-cell identity and plasticity will pave the way for developing more effective strategies,such asβ-cell regeneration therapy,to treat T2D and associated metabolic disorders.

关键词： Type 2 diabetes Pancreaticβ-cell Transcription factors Dedifferentiation Transdifferentiation Redifferentiation

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The SWI/SNF chromatin-remodeling factors BAF60a, b, and c in nutrient signaling and metabolic control

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Protein & Cell 2018年第2期9卷 207-215页

作者： Ruo-Ran Wang Ran Pan Wenjing Zhang Junfen Fu Jiandie D. Lin zhuo-xian meng Department of Pathology and Pathophysiology Key Laboratory of Disease Proteomics of Zhejiang Province School of Medicine Chronic Disease Research Institute of School of Public Health Zhejiang University Hangzhou 310058 China Children's Hospital Zhejiang University School of Medicine Hangzhou 310003 China Life Sciences Institute and Department of Cell & Developmental Biology University of Michigan Medical Center Ann Arbor MI 48109 USA

Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWlISNF *** complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological sigrials. The ATP-dependent SWl/SNF ing complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different m^abolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.

关键词： BAF60a BAF60b BAF60c chromatin- remodeling SWI/SNF energy metabolism nutrient sensing glucose lipid skeletal muscle liver

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Neural innervation in adipose tissue, gut, pancreas, and liver

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Life Metabolism 2023年第4期2卷 22-38页

作者： mengxue Sun Yongwen Wan mengjie Shi zhuo-xian meng Wenwen Zeng Institute for Immunology and School of Medicine Tsinghua Universityand Tsinghua-Peking Center for Life SciencesBeijing 100084China Beijing Key Laboratory for Immunological Research on Chronic Diseases Beijing 100084China Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhouZhejiang 310058China Key Laboratory of Disease Proteomics of Zhejiang Province Zhejiang University School of MedicineHangzhouZhejiang 310058China

Efficient communication between the brain and peripheral organs is indispensable for regulating physiological function and maintaining energy homeostasis. The peripheral nervous system (PNS) in vertebrates, consisting of the autonomic and somatic nervous systems, bridges the peripheral organs and the central nervous system (CNS). Metabolic signals are processed by both vagal sensory nerves and somatosensory nerves. The CNS receives sensory inputs via ascending nerves, serves as the coordination and integration center, and subsequently controls internal organs and glands via descending nerves. The autonomic nervous system consists of sympathetic and parasympathetic branches that project peripheral nerves into various anatomical locations to regulate the energy balance. Sympathetic and parasympathetic nerves typically control the reflexive and involuntary functions in organs. In this review article, we outline the innervation of adipose tissue, gut, pancreas, and liver, to illustrate the neurobiological basis of central-peripheral interactions. We emphasize the importance of understanding the functional atlas of neural control of energy metabolism, and more importantly, provide potential avenues for further research in this area.

关键词： neural innervation peripheral nerves adipose tissue pancreas gut liver

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Intermittent protein restriction protects isletβcells and improves glucose homeostasis in diabetic mice

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Science Bulletin 2022年第7期67卷 733-747页

作者： Siying Wei Chenchen Li Xuemei Luo Lanzexin Yang Long Yu Qintao Wang zhuo-xian meng Tao Wang Yan Chen CAS Key Laboratory of Nutrition Metabolism and Food SafetyShanghai Institute of Nutrition and HealthUniversity of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China Huzhou R&D Center for Nutrition and Health Shanghai Institute of Nutrition and HealthChinese Academy of SciencesHuzhou 313000China Department of Pathology and Pathophysiology Key Laboratory of Precision Diagnosis and Treatment for Hepatobiliary and Pancreatic Tumor of Zhejiang ProvinceFirst Affliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310058China

Diabetes is caused by the interplay between genetics and environmental factors, tightly linked to lifestyle and dietary patterns. In this study, we explored the effectiveness of intermittent protein restriction(IPR)in diabetes control. IPR drastically reduced hyperglycemia in both streptozotocin-treated and leptin receptor-deficient db/db mouse models. IPR improved the number, proliferation, and function of β cells in pancreatic islets. IPR reduced glucose production in the liver and elevated insulin signaling in the skeletal muscle. IPR elevated serum level of FGF21, and deletion of the Fgf21 gene in the liver abrogated the hypoglycemic effect of IPR without affecting β cells. IPR caused less lipid accumulation and damage in the liver than that caused by continuous protein restriction in streptozotocin-treated mice. Single-cell RNA sequencing using mouse islets revealed that IPR reversed diabetes-associated β cell reduction and immune cell accumulation. As IPR is not based on calorie restriction and is highly effective in glycemic control and β cell protection, it has promising translational potential in the future.

关键词： Nutritional intervention Diabetes intervention Protein restriction Islets scRNA-seq

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Comments on‘Dietary intervention preservesβcell function in mice through CTCF-mediated transcriptional reprogramming’

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Journal of Molecular Cell Biology 2022年第7期14卷 76-77页

作者： Ruo-Ran Wang Hongxing Fu Jingya Li zhuo-xian meng School of Pharmaceutical Science and Technology Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China State Key Laboratory of Drug Research the National Center for Drug ScreeningShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Pathology and Pathophysiology and Department of Cardiology of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China Department of Pharmacy Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical CollegeHangzhou 310000China

Type 2 diabetes(T2D)has become a common chronic disease ***βcell dysfunction,together with insulin resistance,is among the main causes for the pathogenesis of ***,the dynamic changes in the number and function ofβcells and the molecular mechanism of irreversible damage in the pathogenesis of T2D are still unclear.A thorough analysis of the mechanism underlyingβcell dysfunction will provide a theoretical basis and molecular targets for the development of new and more effective individualized therapies for diabetes.

关键词： βcell pathogenesis diabetes

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β-cell dynamics in type 2 diabetes and in dietary and exercise interventions

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Journal of Molecular Cell Biology 2022年第7期14卷 1-22页

作者： Chengan Lv Yuchen Sun Zhe Yu Zhang Zeyad Aboelela Xinyuan Qiu zhuo-xian meng Department of Pathology and Pathophysiology and Metabolic Research Center of the Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310003China Key Laboratory of Disease Proteomics of Zhejiang Province Zhejiang University School of MedicineHangzhou 310058China Zhejiang University-University of Edinburgh Institute(ZJE) Zhejiang UniversityHaining 314400China Bachelors of Surgery Bachelors of Medicine(MBBS)Zhejiang University School of MedicineHangzhou 310003China Department of Biology and Chemistry College of Liberal Art and SciencesNational University of Defense TechnologyChangsha 410073China Department of Geriatrics Affiliated Hangzhou First People's HospitalZhejiang University School of MedicineHangzhou 310006China

Pancreaticβ-cell dysfunction and insulin resistance are two of the major causes of type 2 diabetes(T2D).Recent clinical and experimental studies have suggested that the functional capacity ofβ-cells,particularly in the first phase of insulin secretion,is a primary contributor to the progression of T2D and its associated ***β-cells undergo dynamic compensation and decompensation processes during the development of T2D,in which metabolic stresses such as endoplasmic reticulum stress,oxidative stress,and inflammatory signals are key regulators ofβ-cell *** and exercise interventions have been shown to be effective approaches for the treatment of obesity and T2D,especially in the early *** the targeted tissues and underlying mechanisms of dietary and exercise interventions remain somewhat vague,accumulating evidence has implicated the improvement ofβ-cell functional *** this review,we summarize recent advances in the understanding of the dynamic adaptations ofβ-cell function in T2D progression and clarify the effects and mechanisms of dietary and exercise interventions onβ-cell dysfunction in *** review provides molecular insights into the therapeutic effects of dietary and exercise interventions on T2D,and more importantly,it paves the way for future research on the related underlying mechanisms for developing precision prevention and treatment of T2D.

关键词： pancreaticβ-cell type 2 diabetes dietary intervention exercise intervention

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Electrically tunable phase-change metasurface for dynamic infrared thermal camouflage

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Photonics Research 2024年第2期12卷 292-300页

作者： YUFENG XIONG YUNZHENG WANG CHAO FENG YAOLAN TIAN LIANG GAO JUN-LEI WANG ZHUANG zhuo xian ZHAO Center for Optics Research and Engineering Key Laboratory of Laser&Infrared SystemMinistry of EducationShandong UniversityQingdao 266237China School of Information Science and Engineering Shandong UniversityQingdao 266237China

Dynamic infrared thermal camouflage technology has attracted extensive attention due to its ability to thermally conceal targets in various environmental backgrounds by tuning thermal *** use of phase change materials(PCMs)offers numerous advantages,including zero static power,rapid modulation rate,and large emissivity tuning ***,existing PCM solutions still encounter several practical application challenges,such as temperature uniformity,amorphization achievement,and adaptability to different *** this paper,we present the design of an electrically controlled metal-insulator-metal thermal emitter based on a PCM metasurface,and numerically investigate its emissivity tunability,physical mechanisms,heat conduction,and thermal camouflage performance across different ***,the influence of the quench rate on amorphization was studied to provide a guidance for evaluating and optimizing device *** results reveal that the thermal emitter exhibits a wide spectral emissivity tuning range between 8 and 14μm,considerable quench rates for achieving amorphization,and the ability to provide thermal camouflage across a wide background temperature ***,it is anticipated that this contribution will promote the development of PCM-based thermal emitters for practical dynamic infrared thermal camouflage technology with broad applications in both civilian and military domains.

关键词： thermal dynamic phase

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Vulnerability and Conservation of Nearshore Cetaceans to Increasing Vessel Traffic:The Indo-Pacific Humpback Dolphin in the South China Sea

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Journal of Ocean University of China 2024年第4期23卷 1003-1014页

作者： LUO Dingyu GUO Lang HUANG Nuoyan WANG Hongri ZENG Chen TANG Xikai XU zhuo WU Yuping SUN xian School of Marine Sciences Zhuhai Key Laboratory of Marine Bioresources and EnvironmentGuangdong Provincial Key Laboratory of Marine Resources and Coastal EngineeringPearl River Estuary Marine Ecosystem Research Sta-tionMinistry of EducationSun Yat-Sen UniversitySouthern Marine Science and Engineering Guangdong Labora-tory(Zhuhai)Zhuhai 519082China

A comprehensive risk assessment to evaluate the vulnerability of the nearshore cetaceans to increasing marine traffic is *** this study,the risk to Indo-Pacific humpback dolphins(Sousa chinensis)in the main habitats in China was assessed based on a semiquantitative spatial vulnerability analysis.85%of the(sub)population which overlapped with the lanes of ferries and/or cargo vessels,with exposure scores of 1.23±0.31(calculated based on the proportion of sea routes that overlap the dolphin’s range).A combination of high exposure to the sea routes and sensitivity to marine traffic would render the(sub)populations to be highly vulnerable(EPRE:5.21 and XM:4.47).A low frequency of vessels and an awareness of the ecology assures a low vulnerability(SH:2.43,EZ:2.73).Uncertainty scores were commonly lower for the higher vulnerable populations,and higher for the lower vulnerable populations,suggesting additional field data and more monitoring are *** years of field data have been used to analyze the influences of various types of marine traffic on humpback dolphin *** and non-fishing vessels were significantly different(χ^(2)=65.19,p<0.01).The humpback dolphins were attracted by fishing vessels(83.1%)but avoided non-fishing vessels(95.2%).We recommend a management with seasonal and geographical constraints,to balance economic development and environmental conservation.

关键词： Indo-Pacific humpback dolphin vessel impacts risk analysis protection strategy

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CUT&Tag技术在代谢组织细胞的实验操作

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遗传 2022年第10期44卷 958-966页

作者：张子寅周燕萍孟卓贤浙江大学医学院病理学与病理生理学系杭州310058 浙江大学医学院浙江省疾病蛋白质组学重点实验室杭州310058

染色体靶向切割和标签化(clevage under target and tagment,CUT&Tag)技术利用Tn5转座酶与Protein A/G的融合蛋白,引导Tn5酶至与靶蛋白结合的抗体附近,对靶蛋白结合的附近染色质区域进行切割,随后通过标签化处理对片段化染色质进行文库... 详细信息

染色体靶向切割和标签化(clevage under target and tagment,CUT&Tag)技术利用Tn5转座酶与Protein A/G的融合蛋白,引导Tn5酶至与靶蛋白结合的抗体附近,对靶蛋白结合的附近染色质区域进行切割,随后通过标签化处理对片段化染色质进行文库制备,并利用高通量测序技术获取特定位点或蛋白质结合位置的染色质信息。CUT&Tag技术在蛋白质和DNA相互作用的研究领域起到了重大作用,不仅可以了解组蛋白修饰发生的位置,而且可以明确转录因子结合的区域。相较于传统的染色质免疫沉淀高通量测序(chromatin immunoprecipitation-sequencing,ChIP-seq)技术,CUT&Tag技术具有信噪比高、可重复性好、实验周期短、细胞投入量低等优点,在早期胚胎发育、干细胞、肿瘤以及表观遗传学等研究领域体现出巨大优势。本文将针对CUT&Tag在代谢组织细胞(以小鼠原代胰岛细胞为例)的具体操作步骤进行描述,以提供一种研究代谢细胞的表观遗传学方法。

关键词： CUT&Tag 组蛋白修饰操作步骤代谢组织细胞

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