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Ceramides in Metabolism: Key Lipotoxic Players
Annual Review of Physiology ( IF 18.2 ) Pub Date : 2021-02-10 , DOI: 10.1146/annurev-physiol-031620-093815
Bhagirath Chaurasia 1 , Scott A Summers 2
Affiliation  

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.

中文翻译:


新陈代谢中的神经酰胺:关键的脂毒性参与者

2 型糖尿病、脂肪性肝炎、心肌梗塞和中风等代谢性疾病的全球患病率在过去 20 年急剧增加。这些肥胖引发的疾病部分是由于有害脂质代谢物在不适合脂质储存的组织(例如,肝脏、脉管系统、心脏和胰腺β细胞)中的异常积累所致。在积累的众多脂质亚型中,神经酰胺等鞘脂特别具有影响力,因为它们会引发选择性胰岛素抵抗、血脂异常,并最终导致几乎所有代谢紊乱的细胞死亡。这篇综述总结了最近关于控制神经酰胺产生的调节途径的发现,将脂质与这些离散的致病事件联系起来的分子机制,

更新日期:2021-02-11
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