Department of Pediatrics, section Molecular Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Department of Pediatrics, section Molecular Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Mol Metab. 2021 Aug;50:101146. doi: 10.1016/j.molmet.2020.101146. Epub 2021 Jan 5.
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 endoplasmic reticulum (ER).
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.
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.
代谢相关脂肪性肝病（MAFLD），又称非酒精性脂肪性肝病，已成为全球慢性肝病的主要病因。除了肝内甘油三酯蓄积外，胆固醇代谢失调也是 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摄取胆固醇，随后将胆固醇转运至其他膜区室，如内质网（ER）。
内体溶酶体网络对于调节细胞内稳态和适应具有关键作用，新出现的证据表明，内体溶酶体网络对于维持代谢稳态至关重要。在这篇综述中，我们将总结我们对内体溶酶体网络在胆固醇稳态中的作用及其在 MAFLD 发病机制中的意义的现有认识。
尽管已经确定了多种内体溶酶体蛋白在胆固醇摄取、细胞内转运和降解的调节中发挥作用，但它们的生理作用尚不完全清楚。进一步的研究应阐明它们在控制代谢稳态和脂肪性肝病发展中的作用。
