酒精性脂肪性肝炎的脂滴动力学。

IF 3.6 2区 医学 Q1 PATHOLOGY
Delia Y Omar, Mathilda M Willoughby, Nourhan Mostafa, Kelly Otakhor, Saumya Bhatt, Mohammad A Abbas Zaidi, Micah B Schott
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引用次数: 0

摘要

酒精相关肝脏疾病(ALD)是全球重大的健康负担,酒精性脂肪性肝炎(ASH)是一种由慢性酒精摄入、肝脏炎症和有限治疗方案驱动的严重亚型。ASH发病机制的核心是肝细胞脂滴(LD)动力学失调。这篇综述探讨了LD的关键作用,重点是酒精诱导的LD生物发生和分解代谢的破坏。慢性乙醇暴露增强了脂质输入和新生脂肪生成(DNL)的LD生物发生,同时通过抑制脂肪分解和脂肪吞噬来损害LD分解代谢。此外,该综述研究了酒精对LD蛋白质组和脂质组重塑的影响,包括翻译后修饰。此外,ld作为肝星状细胞的形态学标记出现,它们的丢失导致肝纤维化。最近的进展突出了潜在的治疗靶点,如恢复脂肪吞噬或调节LD生物发生,为有效治疗ASH提供了希望。这篇综述强调ld是ASH进展和治疗创新的关键细胞器。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lipid Droplet Dynamics in Alcoholic Steatohepatitis.

Alcohol-associated liver disease poses a significant global health burden, with alcoholic steatohepatitis (ASH) representing a severe subtype driven by chronic alcohol consumption, hepatic inflammation, and limited treatment options. Central to ASH pathogenesis is the dysregulation of lipid droplet (LD) dynamics in hepatocytes. This review explores the critical role of LDs, focusing on alcohol-induced disruptions in LD biogenesis and catabolism. Chronic ethanol exposure enhances LD biogenesis from lipid import and de novo lipogenesis, while impairing LD catabolism by inhibiting lipolysis and lipophagy. Also, the review article examines alcohol's effect on remodeling the LD proteome and lipidome, including post-translational modifications. Additionally, LDs emerge as morphologic markers in hepatic stellate cells, where their loss drives fibrosis. Recent advances highlight potential therapeutic targets, such as restoring lipophagy or modulating LD biogenesis, offering hope for effective ASH treatments. This review underlines LDs as pivotal organelles in ASH progression and therapeutic innovation.

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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
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