Gregor Margaret F, Hotamisligil Gökhan S
Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
J Lipid Res. 2007 Sep;48(9):1905-14. doi: 10.1194/jlr.R700007-JLR200. Epub 2007 May 9.
In the context of obesity and its related maladies, the adipocyte plays a central role in the balance, or imbalance, of metabolic homeostasis. An obese, hypertrophic adipocyte is challenged by many insults, including surplus energy, inflammation, insulin resistance, and considerable stress to various organelles. The endoplasmic reticulum (ER) is one such vital organelle that demonstrates significant signs of stress and dysfunction in obesity and insulin resistance. Under normal conditions, the ER must function in the unique and trying environment of the adipocyte, adapting to meet the demands of increased protein synthesis and secretion, energy storage in the form of triglyceride droplet formation, and nutrient sensing that are particular to the differentiated fat cell. When nutrients are in pathological excess, the ER is overwhelmed and the unfolded protein response (UPR) is activated. Remarkably, the consequences of UPR activation have been causally linked to the development of insulin resistance through a multitude of possible mechanisms, including c-jun N-terminal kinase activation, inflammation, and oxidative stress. This review will focus on the function of the ER under normal conditions in the adipocyte and the pathological effects of a stressed ER contributing to adipocyte dysfunction and a thwarted metabolic homeostasis.
在肥胖及其相关疾病的背景下，脂肪细胞在代谢稳态的平衡或失衡中起着核心作用。肥胖、肥大的脂肪细胞面临着许多损害，包括能量过剩、炎症、胰岛素抵抗以及对各种细胞器的巨大压力。内质网（ER）就是这样一种重要的细胞器，在肥胖和胰岛素抵抗中表现出明显的应激和功能障碍迹象。在正常情况下，内质网必须在脂肪细胞独特且具有挑战性的环境中发挥作用，以适应增加的蛋白质合成与分泌、以甘油三酯滴形成形式进行的能量储存以及分化脂肪细胞特有的营养感知需求。当营养物质处于病理性过剩时，内质网不堪重负，未折叠蛋白反应（UPR）被激活。值得注意的是，UPR激活的后果已通过多种可能机制与胰岛素抵抗的发展存在因果关联，这些机制包括c-jun氨基末端激酶激活、炎症和氧化应激。本综述将聚焦于内质网在正常情况下在脂肪细胞中的功能，以及内质网应激对脂肪细胞功能障碍和代谢稳态紊乱的病理影响。
