Department of Food Science and Human Nutrition, Colorado State University, Fort Collins, CO 80523, USA.
Annu Rev Nutr. 2012 Aug 21;32:17-33. doi: 10.1146/annurev-nutr-071811-150644.
The underlying causes of nonalcoholic fatty liver disease are unclear, although recent evidence has implicated the endoplasmic reticulum in both the development of steatosis and progression to nonalcoholic steatohepatitis. Disruption of endoplasmic reticulum homeostasis, often termed ER stress, has been observed in liver and adipose tissue of humans with nonalcoholic fatty liver disease and/or obesity. Importantly, the signaling pathway activated by disruption of endoplasmic reticulum homeostasis, the unfolded protein response, has been linked to lipid and membrane biosynthesis, insulin action, inflammation, and apoptosis. Therefore, understanding the mechanisms that disrupt endoplasmic reticulum homeostasis in nonalcoholic fatty liver disease and the role of the unfolded protein response in the broader context of chronic, metabolic diseases have become topics of intense investigation. The present review examines the endoplasmic reticulum and the unfolded protein response in the context of nonalcoholic fatty liver disease.
非酒精性脂肪性肝病的根本原因尚不清楚，尽管最近的证据表明内质网在脂肪变性的发展和向非酒精性脂肪性肝炎的进展中都有牵连。内质网稳态的破坏，通常称为内质网应激，在非酒精性脂肪性肝病和/或肥胖症患者的肝脏和脂肪组织中已经观察到。重要的是，由内质网稳态破坏激活的信号通路，即未折叠蛋白反应，与脂质和膜生物合成、胰岛素作用、炎症和细胞凋亡有关。因此，了解破坏非酒精性脂肪性肝病中内质网稳态的机制以及未折叠蛋白反应在慢性代谢性疾病中的更广泛背景下的作用已成为深入研究的课题。本综述探讨了内质网和未折叠蛋白反应在非酒精性脂肪性肝病中的作用。
