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Recent Advances in Understanding Proteins Involved in Lipid Droplet Formation, Growth and Fusion

Journal of Genetics and Genomics 2014年第5期41卷 251-259页

作者： Jolene S.Y.Tan Colin J.P.Seow Vera J.Goh David L.Silver Signature Research Program in Cardiovascular & Metabolic Disorders Duke-NUS Graduate Medical School Singapore

Lipid droplets （LDs） were once viewed as simple, inert lipid micelles. However, they are now known to be organelles with a rich proteome involved in a myriad of cellular processes. LDs are heterogeneous in nature with different sizes and compositions of phospholipids, neutral lipids and proteins. This review takes a focused look at the roles of proteins involved in the regulation of LD formation, expansion, and morphology. The related proteins are summarized such as the fat-specific protein （Fsp27）, fat storage-inducing trans- membrane （FIT） proteins, seipin and ADP-ribosylation factor 1-coat protein complex I （Arf-COPI）. Finally, we present important challenges in LD biology for a deeper understanding of this dynamic organelle to be achieved.

关键词： Lipid droplets LD-associated proteins Perilipin Phospholipids

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WTAP:a new player in postnatal BAT development

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Life Metabolism 2022年第3期1卷 201-202页

作者： Lei Sun Cardiovascular and Metabolic Disorders Program Duke-NUS Medical SchoolSingapore 169857Singapore

Understanding the mechanisms underlying brown fat development and metabolism can provide unique insights into the regulation of energy *** a recent study published in Life Metabolism,Wang et *** Wilms’tumor 1-associating protein(WTAP),a key component in m6A methyltransferase complex,as a new and essential regulator in the postnatal development and maturation of interscapular brown adipose tissue(iBAT).Interscapular brown adipose tissue(iBAT)is the major organ responsible for nonshivering thermogenesis in rodents[1].

关键词： metabolism homeostasis

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The roles of autophagy and thyroid hormone in the pathogenesis and treatment of NAFLD

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肝癌研究（英文版） 2021年第11期7卷 26-41页

作者： Jin Zhou Rohit A.Sinha Paul M.Yen Program of Cardiovascular and Metabolic Disorders Duke-NUS Medical SchoolSingapore 169857Singapore Department of Endocrinology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014India Program of Cardiovascular and Metabolic Disorders Duke-NUS Medical SchoolSingapore 169857Singapore Department of Medicine Duke Molecular Physiology Institute Duke University Medical CenterDurhamNC 27710USA

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disorder worldwide. It comprises simple steatosis and non-alcoholic steatohepatitis (NASH), which can further progress to cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD involves genetic, environmental, and endocrine factors, and several molecular mechanisms have been identified. In this review, we discuss the recent findings on the role of autophagy, in particular lipophagy and mitophagy, in hepatic lipid oxidation. We discuss the pre-clinical and clinical evidence suggesting that impairment of autophagy exacerbates NAFLD progression and restoration of autophagy exerts beneficial effects on NAFLD. We discuss how thyroid hormone (TH) simultaneously regulates lipophagy, mitophagy, and mitochondrial biogenesis to increase β-oxidation of fatty acids and reduce steatosis in the liver. Lastly, we discuss the recent clinical progress in using TH or thyromimetics in treating NAFLD/NASH.

关键词： Autophagy NAFLD lipid oxidation mitophagy thyroid hormone

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Gut microbiota and their metabolites in the progression of non-alcoholic fatty liver disease

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肝癌研究（英文版） 2021年第1期7卷 140-157页

作者： Jin Zhou Madhulika Tripathi Rohit A.Sinha Brijesh Kumar Singh Paul M.Yen Program of Cardiovascular and Metabolic Disorders Duke-NUS Medical SchoolSingapore 169857Singapore Department of Endocrinology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014India Program of Cardiovascular and Metabolic Disorders Duke-NUS Medical SchoolSingapore 169857Singapore Duke Molecular Physiology Institute DurhamNC 27701USA Duke University School of Medicine DurhamNC 27710USA

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver disorder worldwide. It comprises a spectrum of conditions that range from steatosis to non-alcoholic steatohepatitis, with progression to cirrhosis and hepatocellular carcinoma. Currently, there is no FDA-approved pharmacological treatment for NAFLD. The pathogenesis of NAFLD involves genetic and environmental/host factors, including those that cause changes in intestinal microbiota and their metabolites. In this review, we discuss recent findings on the relationship(s) of microbiota signature with severity of NAFLD and the role(s) microbial metabolites in NAFLD progression. We discuss how metabolites may affect NAFLD progression and their potential to serve as biomarkers for NAFLD diagnosis or therapeutic targets for disease management.

关键词： Non-alcoholic fatty liver disease gut microbiome gut microbiota metabolites

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Accelerate the Promotion of Mobile Payments during the COVID-19 Epidemic

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The Innovation 2020年第2期1卷 1-2页

作者： Tuanhui Ren Yu Tang College of Animal Science South China Agricultural UniversityGuangzhouGuangdong 510642China Cardiovascular and Metabolic Disorders Program Duke-NUS Medical SchoolSingapore 169857Singapore School of Government Yunnan UniversityKunmingYunnan 650500China

COVID-19 is caused by a novel SARS-CoV-2(severe acute respiratory syndrome coronavirus 2).During the COVID-19 epidemic,when people are infected with the virus,they can transmit the virus onto paper or coin money through touch and droplets,potentially making any physical currency a carrier of the *** there is no report confirming that people can become infected with viruses by cash circulation,relevant research on the survival of viruses on solid surfaces supports this hy*** payments can help individuals avoid coming in direct contact with any paper or coin ***,we strongly recommend the promotion of mobile payments during the COVID-19 epidemic.

关键词： acute respiratory money

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The co-activator, Mediator subunit(MED1) plays an essential role in hepatic autophagy and lipid oxidation

The co-activator, Mediator subunit(MED1) plays an essential ...

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2018年第二届生物物理学会脂质代谢与生物能学分会年会暨国际学术研讨会

作者： Zhou J Lim A Sinha RA Singh BK Ohba K Yen PM Laboratory of Hormonal Regulation Program of Cardiovascular and Metabolic Disorders Duke-NUS Medical School

MED1 is part of the Mediator complex that functions as a coactivator that bridges RNA polymerase II and basal transcription factors with nuclear receptor co-activator *** MED1-binding nuclear receptors such as thyroid hormone receptor(TR) and peroxisome proliferator atic autophagy and lipid metabolism, it is not known whether MED1 itself has a significant role in these cellular *** the current study,

关键词： Mediator subunit The co-activator plays an essential role in hepatic autophagy and lipid oxidation

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Association between metabolically healthy obesity and atrial fibrillation: A systematic review and meta-analysis of longitudinal studies

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Diabetes and metabolic Syndrome: Clinical Research and Reviews 2025年第4期19卷 103228-103228页

作者： Liu, Xiao Ling, Jitao Wu, Yifan Zhao, Huilei Hu, Yuzhe Yan, Zhiwei Zhu, Wengen Yu, Peng Wang, Jinfeng Zhang, Yuling Bucci, Tommaso Lip, Gregory Y.H. Department of Cardiology Sun Yat-sen Memorial Hospital of Sun Yat-sen University Guangdong Guangzhou China Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology Guangdong Guangzhou China Cardiovascular and Metabolic Disorders Program Duke-National University of Singapore Medical School Singapore Singapore Department of Endocrinology and Metabolism The Second Affiliated Hospital Jiangxi Medical College Nanchang University Jiangxi Nanchang China Anesthesiology Department The Second Affiliated Hospital of Nanchang University Nanchang China Department of Sports Rehabilitation College of Human Kinesiology Shenyang Sport University Shenyang China Department of Cardiology The First Affiliated Hospital of Sun Yat-Sen University Guangdong Guangzhou China Liverpool Centre of Cardiovascular Science at University of Liverpool Liverpool JohnMoores University and Liverpool Heart and Chest Hospital Liverpool United Kingdom Department of General and Specialized Surgery Sapienza University of Rome Rome Italy Danish Center for Health Services Research Department of Clinical Medicine Aalborg University Aalborg Denmark

Introduction: Obesity is not a single diagnosis, and the association of ‘metabolically unhealthy’ obesity with cardiovascular disease is well-described. However, the relationship between metabolically healthy obesity (MHO) and atrial fibrillation (AF) is still debated. Objective: Our objective is to investigate the association between MHO and the risk of AF. Methods: A comprehensive search of databases, including PubMed, EMBASE, Web of Science, and the Cochrane Library regarding longitudinal studies of MHO and risk of AF was performed. Random effects were used to pool the effect estimates. Results: Nine cohort studies comprising 4,250,557 participants were included. The pooled results revealed that individuals with MHO were associated with a greater incidence of AF than those with a metabolically healthy normal weight (HR: 1.34, 95 % CI: 1.26 to 1.42) with moderate certainty according to the Grading of Recommendations Assessment, Development, and Evaluation assessment. Individuals with MHO were associated with a lower risk of AF compared with participants with metabolically unhealthy obesity (RR: 0.48, 95 % CI: 0.36 to 0.64). Individuals with MHO were not significantly associated with the risk of AF as compared to metabolically unhealthy normal weight (HR: 1.04, 95 % CI: 0.89 to 1.22). Conclusion: MHO is associated with a greater incidence of AF, highlighting the importance of weight reduction in individuals without metabolic disorders in reducing the risk of AF. Registration: PROSPERO - registration number CRD42023432195. © 2025 Research Trust of DiabetesIndia (DiabetesIndia) and National Diabetes Obesity and Cholesterol Foundation (N-DOC)

关键词： Atrial fibrillation Meta-analysis metabolically healthy obesity metabolically unhealthy obesity Obesity

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Thyroid hormone regulation of mitochondrial activity,mitophagy,and biogenesis in liver

Thyroid hormone regulation of mitochondrial activity,mitopha...

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全球华人生物学家大会暨第十六届美洲华人生物科学学会学术研讨会

作者： Paul M.Yen Laboratory of Hormonal Regulation Cardiovascular and Metabolic Disorders ProgramDuke-NUS Graduate Medical School

Thyroid hormone(TH)plays critical roles in carbohydrate and lipid *** previously showed that TH stimulates autophagy of lipid droplets in the liver to increase beta-oxidation of fatty acids and oxidative phosphorylati... 详细信息

关键词： Thyroid hormone regulation of mitochondrial activity,mitophagy,and biogenesis in liver

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FoxO1 deacetylation mediates thyroid hormone action on hepatic gluconeogenic genes by a novel mechanism

FoxO1 deacetylation mediates thyroid hormone action on hepat...

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2013年全球华人生物科学家大会

作者： Brijesh Kumar Singh Rohit Anthony Sinha in Zhou Paul Michael Yen Laboratory of Hormonal Regulation Cardiovascular and Metabolic Disorders ProgramDuke-NUS Graduate Medical SchoolSingapore 169857

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A comprehensive cardiotoxicity assay by combining high-throughput multiple ion channel screening with human cardiomyocyte-based action potential validation

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中国药理学与毒理学杂志 2015年第S1期29卷 31-32页

作者： He-mingWEI Jian-junWU YingYingCHUNG CaiHongKOH Zhen-fengLIU StuartCOOK WinstonSHIM TanMeiLAN National Heart Research Institute Singapore National Heart Centre Singapore Singapore 169609 Singapore Cardiovascular & Metabolic Disorders Program Duke-NUS Graduate Medical School Singapore 169857 Singapore Malaysian Institute of Pharmaceuticals and Nutraceuticals Halaman Bukit Gambir 11700 Pulau Pinang Malaysia

OBJECTIVE Cardiotoxicity refers to drug-induced arrhythmia such as Torsades de *** single ion channel(hERG)-based assay generates-30% false *** aim is to establish an advanced in vitro cardiotoxicity assay by incorporating high throughput multiple cardiac ion channel screening and human cardiomyocytes-based *** Effects of drugs were tested on multiple cell lines expressing hERG,Nav1.5 and Cav1.2 by automated patch ***,the results were validated with human pluripotent stem cell(hPSC)-derived cardiomyocytes(hPSC-CMs)in which ion currents and action potentials were measured by manual patch *** We have tested the cardiotoxicity of monomers extracted from various medical *** is the major bioactive compound isolated from kratom,a therapeutic herb from the rain forest of South East *** a popular stimulant,it has been associated with a number of acute fatal *** observed a typical torsadogenic hazard of *** exerted a strong hERG inhibition in hERG-HEK293 cell line(IC50:5.2 μmol·L-1)and hPSC-CMs(IC50:0.91 μmol·L-1)without affecting other cardiac ion ***,it caused a significant prolongation of action potential duration(APD)in hPSC-CMs(a-32.5%increase in APD at 50 and 90%repolarization).On the other hand,deoxylelephantopin,apotential anti-cancer reagent,demonstrated low *** exerted a week inhibition on hERG in HEK293 cells with an IC50 of 87.2 μmol·L-1,while the effective concentrations for suppressing the growth of cancer cells ranges from 2 to 20μmol·*** 100μmol·L-1,deoxylelephantopin showed no effects on Cav1.2 and Nav1.5 and it failed to alter APD in *** We have successfully tested a newin vitro cardiotoxicity assay strategy which incorporates multiple cardiac ion channels screening and hPSC-CMs *** new strategy could facilitate the effective and efficient evaluation of existing and new drugs/reagents for potenti

关键词： cardiotoxicity ion channels action potentials card

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