{"title":"神经酰胺在代谢中的作用:主要的脂毒性参与者。","authors":"Bhagirath Chaurasia, Scott A Summers","doi":"10.1146/annurev-physiol-031620-093815","DOIUrl":null,"url":null,"abstract":"The global prevalence of metabolic diseases such as type 2 diabetes mellitus, steatohepatitis, myocardial infarction, and stroke has increased dramatically over the past two decades. These obesity-fueled disorders result, in part, from the aberrant accumulation of harmful lipid metabolites in tissues not suited for lipid storage (e.g., the liver, vasculature, heart, and pancreatic beta-cells). Among the numerous lipid subtypes that accumulate, sphingolipids such as ceramides are particularly impactful, as they elicit the selective insulin resistance, dyslipidemia, and ultimately cell death that underlie nearly all metabolic disorders. This review summarizes recent findings on the regulatory pathways controlling ceramide production, the molecular mechanisms linking the lipids to these discrete pathogenic events, and exciting attempts to develop therapeutics to reduce ceramide levels to combat metabolic disease. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.","PeriodicalId":8196,"journal":{"name":"Annual review of physiology","volume":null,"pages":null},"PeriodicalIF":15.7000,"publicationDate":"2021-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-physiol-031620-093815","citationCount":"87","resultStr":"{\"title\":\"Ceramides in Metabolism: Key Lipotoxic Players.\",\"authors\":\"Bhagirath Chaurasia, Scott A Summers\",\"doi\":\"10.1146/annurev-physiol-031620-093815\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The global prevalence of metabolic diseases such as type 2 diabetes mellitus, steatohepatitis, myocardial infarction, and stroke has increased dramatically over the past two decades. These obesity-fueled disorders result, in part, from the aberrant accumulation of harmful lipid metabolites in tissues not suited for lipid storage (e.g., the liver, vasculature, heart, and pancreatic beta-cells). Among the numerous lipid subtypes that accumulate, sphingolipids such as ceramides are particularly impactful, as they elicit the selective insulin resistance, dyslipidemia, and ultimately cell death that underlie nearly all metabolic disorders. This review summarizes recent findings on the regulatory pathways controlling ceramide production, the molecular mechanisms linking the lipids to these discrete pathogenic events, and exciting attempts to develop therapeutics to reduce ceramide levels to combat metabolic disease. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.\",\"PeriodicalId\":8196,\"journal\":{\"name\":\"Annual review of physiology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":15.7000,\"publicationDate\":\"2021-02-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1146/annurev-physiol-031620-093815\",\"citationCount\":\"87\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annual review of physiology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1146/annurev-physiol-031620-093815\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2020/11/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of physiology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-physiol-031620-093815","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2020/11/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
The global prevalence of metabolic diseases such as type 2 diabetes mellitus, steatohepatitis, myocardial infarction, and stroke has increased dramatically over the past two decades. These obesity-fueled disorders result, in part, from the aberrant accumulation of harmful lipid metabolites in tissues not suited for lipid storage (e.g., the liver, vasculature, heart, and pancreatic beta-cells). Among the numerous lipid subtypes that accumulate, sphingolipids such as ceramides are particularly impactful, as they elicit the selective insulin resistance, dyslipidemia, and ultimately cell death that underlie nearly all metabolic disorders. This review summarizes recent findings on the regulatory pathways controlling ceramide production, the molecular mechanisms linking the lipids to these discrete pathogenic events, and exciting attempts to develop therapeutics to reduce ceramide levels to combat metabolic disease. Expected final online publication date for the Annual Review of Physiology, Volume 83 is February 10, 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
期刊介绍:
Since 1939, the Annual Review of Physiology has been highlighting significant developments in animal physiology. The journal covers diverse areas, including cardiovascular physiology, cell physiology, ecological, evolutionary, and comparative physiology, endocrinology, gastrointestinal physiology, neurophysiology, renal and electrolyte physiology, respiratory physiology, and special topics.