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脂滴与肝脏疾病:从基础生物学到临床意义

Lipid droplets and liver disease: from basic biology to clinical implications.

作者信息

Gluchowski Nina L, Becuwe Michel, Walther Tobias C, Farese Robert V

机构信息

Department of Genetics and Complex Diseases, Harvard T. H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, USA.

Boston Children's Hospital Department of Gastroenterology, Hepatology and Nutrition, 300 Longwood Avenue Boston, Massachusetts 02115, USA.

出版信息

Nat Rev Gastroenterol Hepatol. 2017 Jun;14(6):343-355. doi: 10.1038/nrgastro.2017.32. Epub 2017 Apr 21.

Abstract

Lipid droplets are dynamic organelles that store neutral lipids during times of energy excess and serve as an energy reservoir during deprivation. Many prevalent metabolic diseases, such as the metabolic syndrome or obesity, often result in abnormal lipid accumulation in lipid droplets in the liver, also called hepatic steatosis. Obesity-related steatosis, or NAFLD in particular, is a major public health concern worldwide and is frequently associated with insulin resistance and type 2 diabetes mellitus. Here, we review the latest insights into the biology of lipid droplets and their role in maintaining lipid homeostasis in the liver. We also offer a perspective of liver diseases that feature lipid accumulation in these lipid storage organelles, which include NAFLD and viral hepatitis. Although clinical applications of this knowledge are just beginning, we highlight new opportunities for identifying molecular targets for treating hepatic steatosis and steatohepatitis.

摘要

脂滴是动态细胞器,在能量过剩时储存中性脂质,并在能量缺乏时作为能量储备。许多常见的代谢性疾病,如代谢综合征或肥胖症,常常导致肝脏脂滴中脂质异常蓄积,即肝脂肪变性。与肥胖相关的脂肪变性,尤其是非酒精性脂肪性肝病(NAFLD),是全球主要的公共卫生问题,且常与胰岛素抵抗和2型糖尿病相关。在此,我们综述了脂滴生物学的最新见解及其在维持肝脏脂质稳态中的作用。我们还展望了以这些脂质储存细胞器中脂质蓄积为特征的肝脏疾病,包括NAFLD和病毒性肝炎。尽管这方面知识的临床应用才刚刚起步,但我们强调了识别治疗肝脂肪变性和脂肪性肝炎分子靶点的新机会。

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本文引用的文献

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Lipid droplet hijacking by intracellular pathogens.细胞内病原体对脂滴的劫持
Cell Microbiol. 2017 Jan;19(1). doi: 10.1111/cmi.12688. Epub 2016 Nov 21.
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The physics of lipid droplet nucleation, growth and budding.脂滴的成核、生长和出芽的物理学
Biochim Biophys Acta. 2016 Aug;1861(8 Pt A):715-22. doi: 10.1016/j.bbalip.2016.04.018. Epub 2016 Apr 27.
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Epidemiology and natural history of non-alcoholic fatty liver disease.非酒精性脂肪性肝病的流行病学与自然史
Metabolism. 2016 Aug;65(8):1017-25. doi: 10.1016/j.metabol.2016.01.012. Epub 2016 Jan 29.
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Targeting Fat: Mechanisms of Protein Localization to Lipid Droplets.靶向脂肪:蛋白质定位于脂滴的机制
Trends Cell Biol. 2016 Jul;26(7):535-546. doi: 10.1016/j.tcb.2016.02.007. Epub 2016 Mar 16.

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