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Food Science and Human Wellness 2024年第3期13卷 1672-1684页

作者： Ling Zhang Wenyu Zou Yongyan Hu Honghua Wu Ying Gao Junqing Zhang Jia Zheng Department of endocrinology Peking University First HospitalBeijing 100034China laboratory animal Facility Peking University First HospitalBeijing 100034China

Exercise training is critical for the early prevention and treatment of obesity and diabetes ***,the mechanism with gut microbiota and fecal metabolites underlying the effects of voluntary wheel running on high-fat diet induced abnormal glucose metabolism has not been fully elaborated.C57BL/6 male mice were randomly assigned to 4 groups according to diets(fed with normal chow diet or high-fat diet)and running paradigm(housed in static cage or with voluntary running wheel).An integrative 16S rDNA sequencing and metabolites profiling was synchronously performed to characterize the effects of voluntary wheel running on gut microbiota and *** showed that voluntary wheel running prevented the detrimental effects of high-fat feeding on glucose metabolism 16S rDNA sequencing showed remarkable changes in Rikenella and Marvinbryantia *** profiling indicated multiple altered metabolites,which were enriched in secondary bile acid biosynthesis *** conclusion,our study indicated that voluntary wheel running significantly improved glucose metabolism and counteracted the deleterious effects of high-fat feeding on body weight and glucose *** further found that voluntary wheel running could integratively program gut microbiota composition and fecal metabolites changes,and may regulate muricholic acid metabolism and secondary bile acid biosynthesis in high-fat fed mice.

关键词： High-fat diet Voluntary wheel running Gut microbiota Metabolomics Glucose metabolism

TBC1D1 is an energy-responsive polarization regulator of macrophages via governing ROS production in obesity

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Science China(Life Sciences) 2024年第9期67卷 1899-1914页

作者： Qi Wang Ping Rong Wen Zhang Xinyu Yang Liang Chen Ye Cao Minjun Liu Weikuan Feng Qian Ouyang Qiaoli Chen Hailong Li Hui Liang Fanguo Meng Hong-Yu Wang Shuai Chen State Key laboratory of Pharmaceutical Biotechnology Department of CardiologyNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolModel Animal Research CenterSchool of MedicineNanjing UniversityNanjing 210061China MOE Key laboratory of Model animal for Disease Study Department of EndocrinologyNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolModel Animal Research CenterSchool of MedicineNanjing UniversityNanjing 210061China College of Life Science Anhui Medical UniversityHefei 230032China Redox Medical Center for Public Health Medical College of Soochow UniversitySuzhou 215123China Department of General Surgery First Affiliated HospitalNanjing Medical UniversityNanjing 210029China

Energy status is linked to the production of reactive oxygen species(ROS)in macrophages,which is elevated in ***,it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of ***,we show that the Rab-GTPase activating protein(Rab GAP)TBC1D1,a substrate of the energy sensor AMP-activated protein kinase(AMPK),is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity ***1D1 deletion decreases,whereas an energy overload-mimetic non-phosphorylatable TBC1D1^(S231A)Amutation increases,ROS production and M1-like polarization in ***,TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS *** of TBC1D1^(S231A)bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable Tt SOD for removal of ROS selectively in macrophages alleviates both TBC1D1~(S231A)mutation-and diet-induced *** findings therefore have implications for drug discovery to combat obesity.

关键词： TBC1D1 AMPK Rab8a NOX2 ROS inflammation macrophage obesity

Allelic reprogramming of chromatin states in human early embryos

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National Science Review 2024年第3期11卷 58-71页

作者： Shenli Yuan Lei Gao Wenrong Tao Jianhong Zhan Gang Lu Jingye Zhang Chuanxin Zhang Lizhi Yi Zhenbo Liu Zhenzhen Hou Min Dai Han Zhao Zi-Jiang Chen Jiang Liu Keliang Wu Center for Reproductive Medicine Shandong University CAS Key laboratory of Genome Sciences and Information Collaborative Innovation Center of Genetics and Development Beijing Institute of Genomicsand China National Center for BioinformationChinese Academy of Sciences University of Chinese Academy of Sciences CUHK-SDU Joint laboratory on Reproductive Genetics School of Biomedical Sciences the Chinese University of Hong Kong Key laboratory of Reproductive endocrinology of the Ministry of Education Shandong University Center for Reproductive Medicine Ren Ji Hospital School of Medicine Shanghai Jiao Tong University CAS Center for Excellence in animal Evolution and Genetics Chinese Academy of Sciences

The reprogramming of parental epigenomes in human early embryos remains elusive. To what extent the characteristics of parental epigenomes are conserved between humans and mice is currently unknown. Here,we mapped parental haploid epigenomes using human parthenogenetic and androgenetic embryos. Human embryos have a larger portion of genome with parentally specific epigenetic states than mouse *** allelic patterns of epigenetic states for orthologous regions are not conserved between humans and mice. Nevertheless, it is conserved that maternal DNA methylation and paternal H3K27me3 are associated with the repression of two alleles in humans and mice. In addition, for DNA-methylation-dependent imprinting, we report 19 novel imprinted genes and their associated germline differentially methylated regions. Unlike in mice, H3K27me3-dependent imprinting is not observed in human early ***, allele-specific epigenomic reprogramming is different in humans and mice.

关键词： human embryo epigenetics reprogramming DNA methylation H3K27me3 chromatin accessibility

Pathological mechanism of immune disorders in diabetic kidney disease and intervention strategies

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World Journal of Diabetes 2024年第6期15卷 1111-1121页

作者： Tong Zhou Yi-Lin Fang Tian-Tian Tian Gui-Xia Wang Department of endocrinology and Metabolism The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina Key laboratory of Organ Regeneration and Transplantation of the Ministry of Education The First Hospital of Jilin UniversityChangchun 130021Jilin ProvinceChina National-Local Joint Engineering laboratory of animal Models for Human Diseases Jilin UniversityChangchun 130021Jilin ProvinceChina School of Public Health Jilin UniversityChangchun 130021Jilin ProvinceChina

Diabetic kidney disease is one of the most severe chronic microvascular complications of diabetes and a primary cause of end-stage renal *** studies have shown that renal inflammation is a key factor determining kidney damage during *** the development of immunological technology,many studies have shown that diabetic nephropathy is an immune complex disease,and that most patients have immune ***,the immune response associated with diabetic nephropathy and autoimmune kidney disease,or caused by ischemia or infection with acute renal injury,is different,and has a complicated pathological *** this review,we discuss the pathogenesis of diabetic nephropathy in immune disorders and the intervention mechanism,to provide guidance and advice for early intervention and treatment of diabetic nephropathy.

关键词： Diabetic kidney disease Immune disorders Pathological mechanism Intervention strategy Kidney damage Diabetic nephropathy Inflammasome Immunoglobulin

Influence of ear tags on the results of body composition analysis in mice

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animal Models and Experimental Medicine 2024年第4期7卷 578-583页

作者： He Liu Yinghua Zhang Peng Zhang Weiping Teng Zhongyan Shan Yushu Li Dan Wang Department of endocrinology and Metabolism and the Institute of endocrinology NHC Key Laboratory of Diagnosis and Treatment of Thyroid DiseasesThe First Hospital of China Medical UniversityShenyangChina School of Public Health China Medical University China Medical UniversityShenyangChina Shenyang Food and Drug Inspection Institute ShenyangChina

Background:The aim of this study was to investigate the influence of marking meth-ods on the outcomes of body composition analysis and provide guidance for the se-lection of marking methods in mouse body composition ***:Male C57BL/6J mice aged 6 weeks were randomly assigned for pre-and post-ear tagging *** body composition of the mice was measured using a small animal body composition analyzer,which provided measurements of the mass of fat,lean,and free ***,the mass of fat,lean and free fluid to body weight ratio was *** data analysis was conducted to obtain the range and coeffi-cient of variation in body composition measurements for each *** distribution of fat and lean tissue in the mice was also analyzed by comparing the fat-to-lean ***:(1)The mass of all body composition components in the ear tagging group was significantly lower than that in the control group.(2)There was a significant in-crease in the range and coefficient of variation of body composition measurements between the ear tagging group and the control group.(3)The fat-to-lean ratio in the ear tagging group was significantly lower than that in the control ***:Ear tagging significantly lowered the results of body composition analy-sis in mice and higher the results of measurement ***,ear tagging should be avoided as much as possible when conducting body composition analysis experi-ments in mice.

关键词： body composition analysis ear tagging labeling method stainless steel toe clipping

Dynamic changes in butyrate levels regulate satellite cell homeostasis by preventing spontaneous activation during aging

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Science China(Life Sciences) 2024年第4期67卷 745-764页

作者： Shujie Chen Liujing Huang Bingdong Liu Huimin Duan Ze Li Yifan Liu Hu Li Xiang Fu Jingchao Lin Yinlan Xu Li Liu Dan Wan Yulong Yin Liwei Xie Department of endocrinology and Metabolism Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China State Key laboratory of Applied Microbiology Southern China Guangdong Provincial Key Laboratory of Microbial Culture Collection and ApplicationGuangdong Open Laboratory of Applied MicrobiologyInstitute of MicrobiologyGuangdong Academy of SciencesGuangzhou 510070China School of Public Health Xinxiang Medical UniversityXinxiang 453003China Department of Infectious Diseases Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Metabo-Profile Biotechnology(Shanghai)Co.Ltd. Shanghai 201315China Institute of Aging Research Guangdong Provincial Key Laboratory of Medical Molecular DiagnosticsSchool of Medical TechnologyGuangdong Medical UniversityDongguan 524023China Department of Rehabilitation Medicine Nanfang HospitalSouthern Medical UniversityGuangzhou 510000China laboratory of animal Nutritional Physiology and Metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical RegionInstitute of Subtropical AgricultureChinese Academy of SciencesChangsha 410125China Bioland laboratory Guangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhou 510005China

The gut microbiota plays a pivotal role in systemic metabolic processes and in particular functions,such as developing and preserving the skeletal muscle ***,the interplay between gut microbiota/metabolites and the regulation of satellite cell(SC)homeostasis,particularly during aging,remains *** propose that gut microbiota and its metabolites modulate SC physiology and homeostasis throughout skeletal muscle development,regeneration,and aging *** investigation reveals that microbial dysbiosis manipulated by either antibiotic treatment or fecal microbiota transplantation from aged to adult mice,leads to the activation of SCs or a significant reduction in the total ***,employing multi-omics(e.g.,RNA-seq,16S r RNA gene sequencing,and metabolomics)and bioinformatic analysis,we demonstrate that the reduced butyrate levels,alongside the gut microbial dysbiosis,could be the primary factor contributing to the reduction in the number of SCs and subsequent impairments during skeletal muscle ***,butyrate supplementation can mitigate the antibiotics-induced SC activation irrespective of gut microbiota,potentially by inhibiting the proliferation and differentiation of SCs/*** butyrate effect is likely facilitated through the monocarboxylate transporter 1(Mct1),a lactate transporter enriched on membranes of SCs and *** a result,butyrate could serve as an alternative strategy to enhance SC homeostasis and function during skeletal muscle *** findings shed light on the potential application of microbial metabolites in maintaining SC homeostasis and preventing skeletal muscle aging.

关键词： gut microbiota aging satellite cells butyrate Slc16a1(Mct1)

Alternate day fasting aggravates atherosclerosis through the suppression of hepatic ATF3 in Apoe^(-/-)mice

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Life Metabolism 2024年第3期3卷 46-59页

作者： Yajuan Deng Xiaoyu Yang Xueru Ye Youwen Yuan Yanan Zhang Fei Teng Danming You Xuan Zhou Wenhui Liu Kangli Li Shenjian Luo Zhi Yang Ruxin Chen Guojun Shi Jin Li Huijie Zhang Department of endocrinology and Metabolism Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Guangdong Provincial Key laboratory of Shock and Microcirculation Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China State Key laboratory of Organ Failure Research National Clinical Research Center for Kidney DiseaseNanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of endocrinology The Second Hospital of Shanxi Medical UniversityShanxi Medical UniversityTaiyuanShanxi 030001China Department of endocrinology and Metabolism Guangdong Provincial Key Laboratory of DiabetologyThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China

Atherosclerosis is the major contributor to cardiovascular mortality *** day fasting(ADF)has gained growing attention due to its metabolic ***,the effects of ADF on atherosclerotic plaque formation remain inconsistent and controversial in atherosclerotic animal *** present study was designed to investigate the effects of ADF on atherosclerosis in apolipoprotein E-deficient(Apoe^(-/-))***-week-old male Apoe^(-/-)mice fed with Western diet(WD)were randomly grouped into ad libitum(AL)group and ADF group,and ADF aggravated both the early and advanced atherosclerotic lesion formation,which might be due to the disturbed cholesterol profiles caused by ADF *** significantly altered cholesterol metabolism pathways and down-regulated integrated stress response(ISR)in the *** hepatic expression of activating transcription factor 3(ATF3)was suppressed in mice treated with ADF and hepatocyte-specific overexpression of Aft3 attenuated the effects of ADF on atherosclerotic plaque formation in Apoe^(-/-)***,the expression of ATF3 could be regulated by Krüppel-like factor 6(KLF6)and both the expressions of ATF3 and KLF6 were regulated by hepatic cellular ISR *** conclusion,ADF aggravates atherosclerosis progression in Apoe^(-/-)mice fed on *** inhibits the hepatic ISR signaling pathway and decreases the expression of KLF6,subsequently inhibiting ATF3 *** suppressed ATF3 expression in the liver mediates the deteriorated effects of ADF on atherosclerosis in Apoe^(-/-)*** findings suggest the potentially harmful effects when ADF intervention is applied to the population at high risk of atherosclerosis.

关键词： alternate day fasting atherosclerosis cholesterol integrated stress response activating transcription factor 3

A novel mouse model of calcific aortic valve stenosis

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animal Models and Experimental Medicine 2024年第4期7卷 523-532页

作者： Ningjing Qian Yaping Wang Wangxing Hu Naifang Cao Yi Qian Jinyong Chen Juan Fang Dilin Xu Haochang Hu Shuangshuang Yang Dao Zhou Hanyi Dai Dongdong Wei Jian'an Wang Xianbao Liu Department of Cardiology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina State Key laboratory of Transvascular Implantation Devices China Cardiovascular Key laboratory of Zhejiang Province HangzhouChina Department of Cardiovascular Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Department of endocrinology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Binjiang Institute of Zhejiang University HangzhouChina

Background:Calcific aortic valve stenosis(CAVS)is one of the most challenging heart diseases in clinical with rapidly increasing ***,study of the mecha-nism and treatment of CAVS is hampered by the lack of suitable,robust and efficient models that develop hemodynamically significant stenosis and typical calcium ***,we aim to establish a mouse model to mimic the development and features of ***:The model was established via aortic valve wire injury(AVWI)combined with vitamin D subcutaneous injected in wild type C57/BL6 *** transthoracic echocardiography was applied to evaluate aortic jet peak velocity and mean *** specimens were collected and examined in respect of valve thickening,calcium deposition,collagen accumulation,osteogenic differentiation and ***:Serial transthoracic echocardiography revealed that aortic jet peak velocity and mean gradient increased from 7 days post model establishment in a time depend-ent manner and tended to be stable at 28 *** with the sham group,sim-ple AVWI or the vitamin D group,the hybrid model group showed typical pathological features of CAVS,including hemodynamic alterations,increased aortic valve thicken-ing,calcium deposition,collagen accumulation at 28 *** addition,osteogenic dif-ferentiation,fibrosis and inflammation,which play critical roles in the development of CAVS,were observed in the hybrid ***:We established a novel mouse model of CAVS that could be induced efficiently,robustly and economically,and without genetic *** provides a fast track to explore the underlying mechanisms of CAVS and to identify more effec-tive pharmacological targets.

关键词： animal model calcific aortic valve stenosis valve calcification

Diabetic cardiomyopathy:Emerging therapeutic options

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World Journal of Diabetes 2024年第8期15卷 1677-1682页

作者： Cornelius James Fernandez Sahana Shetty Joseph M Pappachan Department of endocrinology&Metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of endocrinology Kasturba Medical CollegeManipal Academy of Higher EducationManipal 576104KarnatakaIndia Department of endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

Diabetic cardiomyopathy(DbCM)is a common but underrecognized complication of patients with diabetes mellitus(DM).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options,the mechanisms and management options for DbCM are still not fully *** its early stages,DbCM presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately *** from prompt control of DM with lifestyle changes and antidiabetic medications,disease-modifying therapy for DbCM includes prompt control of hypertension and dyslipidemia inherent to patients with DM as in other forms of heart diseases and the use of treatments with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic mouse models with *** this preliminary basic study might help to improve our understanding of DbCM and offer a potential new management option for patients with the disease,the positive results from such animal models might not always translate to clinical practice as the pathobiology of DbCM in humans could be ***,such experimental studies can encourage more scientific efforts to find a better solution to treat patients with this enigmatic disease.

关键词： Diabetic cardiomyopathy Diabetic cardiomyopathy Heart failure Pathobiology Teneligliptin

Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders

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Science China(Life Sciences) 2024年第6期67卷 1170-1182页

作者： Jiaming Liu Liangkui Li Dijin Xu Yuqi Li Tao Chen Yeyang Liu Yuqian Bao Yan Wang Longyan Yang Peng Li Li Xu State Key laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences Beijing Advanced Innovation Center for Structural BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Shanghai Qi Zhi Institute Shanghai 200232China Shanghai Key laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Tianjian laboratory of Advanced Biomedical Sciences Zhengzhou UniversityZhengzhou 450001China Department of Physiology School of Basic Medical SciencesGannan Medical UniversityGanzhou 341000China Department of endocrinology and Metabolism Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s HospitalShanghai 200025China Center for Endocrine Metabolism and Immune Diseases Beijing Luhe HospitalCapital Medical UniversityBeijing 101149China Beijing Key laboratory of Diabetes Research and Care Beijing 101149China

Metabolically healthy obesity refers to obese individuals who do not develop metabolic *** people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecules participating in this specific scenario remain ***18,a lipid droplet(LD)-associated protein,mediates the contact between the endoplasmic reticulum(ER)and LDs to facilitate LD growth and *** the present study,we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and ***18 adipocyte-specific knockout(Rab18 AKO)mice had a decreased volume ratio of SAT to VAT compared with wildtype *** subjected to high-fat diet(HFD),Rab18 AKO mice had increased ER stress and inflammation,reduced adiponectin,and decreased triacylglycerol(TAG)accumulation in *** contrast,TAG accumulation in VAT,brown adipose tissue(BAT)or liver of Rab18AKO mice had a moderate increase without ER stress ***18 AKO mice developed insulin resistance and systematic ***18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart ***,Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,indicating the involvement of Rab18 in alleviating lipid ***18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired *** conclusion,our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

关键词： Rab18 subcutaneous adipose tissue(SAT) metabolically healthy obesity(MHO) lipotoxicity ER stress ectopic lipid storage LD-ER contact