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

我们已经揭示了一个共同的伴侣，Sdf21，在一个refed状态在肝脏中的作用。我们进一步关注与BiP的相互作用，BiP是一种在内质网（ER）中起关键作用的伴侣，在肝细胞内质网（ER）应激下，BiP升高。然而，在肥胖和糖尿病的小鼠模型中，Sdf2l1在肝脏中的表达在转录水平上下调，表明其病理生理学重要性通过不能响应过度的ER应激。实际上，成年小鼠中Sdf2l1的消融显示出与暂时敲除该基因的小鼠相似的表型，我们之前分析过，进一步的证据表明肝脏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.