Background

Metabolic-associated fatty liver disease (MAFLD), also known as non-alcoholic fatty liver disease, has become the leading cause of chronic liver disease worldwide. In addition to hepatic accumulation of triglycerides, dysregulated cholesterol metabolism is an important contributor to the pathogenesis of MAFLD. Maintenance of cholesterol homeostasis is highly dependent on cellular cholesterol uptake and, subsequently, cholesterol transport to other membrane compartments, such as the endocytic reticulum (ER).

Scope of review

The endolysosomal network is key for regulating cellular homeostasis and adaptation, and emerging evidence has shown that the endolysosomal network is crucial to maintain metabolic homeostasis. In this review, we will summarize our current understanding of the role of the endolysosomal network in cholesterol homeostasis and its implications in MAFLD pathogenesis.

Major conclusions

Although multiple endolysosomal proteins have been identified in the regulation of cholesterol uptake, intracellular transport, and degradation, their physiological role is incompletely understood. Further research should elucidate their role in controlling metabolic homeostasis and development of fatty liver disease.

中文翻译：

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内溶酶体网络在胆固醇稳态和代谢相关脂肪肝疾病 (MAFLD) 中的作用

背景

代谢相关性脂肪肝病（MAFLD），也称为非酒精性脂肪肝病，已成为全球慢性肝病的主要原因。除了甘油三酯的肝脏积累外，胆固醇代谢失调是 MAFLD 发病机制的重要因素。胆固醇稳态的维持高度依赖于细胞胆固醇的摄取，以及随后胆固醇转运到其他膜区室，例如内吞网 (ER)。

审查范围

内溶酶体网络是调节细胞稳态和适应的关键，新出现的证据表明内溶酶体网络对于维持代谢稳态至关重要。在这篇综述中，我们将总结我们目前对内溶酶体网络在胆固醇稳态中的作用及其在 MAFLD 发病机制中的影响的理解。

主要结论

尽管已在胆固醇摄取、细胞内转运和降解的调节中鉴定出多种内溶酶体蛋白，但它们的生理作用尚不完全清楚。进一步的研究应该阐明它们在控制代谢稳态和脂肪肝疾病发展中的作用。