Response to feeding-induced endoplasmic reticulum stress in the liver regulated by Sdf2l1 maintains glucose and lipid homeostasis

我们已经揭示了一种共同伴侣，Sdf21，在肝脏中的调节状态下的作用。我们进一步关注了与BiP的相互作用，BiP是一种在内质网（ER）中起关键作用的伴侣蛋白，在肝细胞内质网（ER）应激下升高。然而，在肥胖和糖尿病小鼠模型中，肝脏中Sdf2l1的表达在转录水平上下调，表明其通过无法对过度内质网应激做出反应而具有病理生理重要性。实际上，成年小鼠中Sdf2l1的消融显示出与该基因暂时缺失的小鼠相似的表型，我们之前分析过，这进一步证明了肝脏Sdf2l1在维持全身葡萄糖和脂质稳态中的重要性。

We have revealed the role of a co-chaperone, Sdf21, in a refed state in the liver. We further focused on interaction with BiP, a chaperone playing a pivotal role in endoplasmic reticulum (ER), which was elevated under endoplasmic reticulum (ER) stress in hepatocytes. In a mouse model of obesity and diabetes, however, expression of Sdf2l1 in the liver was down-regulated at the level of transcription, suggesting its pathophysiological importance via inability to respond to excessive ER stress. Actually ablation of Sdf2l1 in adult mice showed phenotypes similar to those in mice with the gene knocked down temporarily, which we analyzed before, adding further evidence to indicate the importance of hepatic Sdf2l1 in maintenance of systemic glucose and lipid homeostasis.