Department of Internal Medicine, State University of Campinas, Campinas, SP, Brazil.
Obesity (Silver Spring). 2013 Dec;21(12):2452-7. doi: 10.1002/oby.20410. Epub 2013 Jun 11.
The double-stranded RNA-dependent protein kinase (PKR) was recently implicated in regulating molecular integration of nutrient- and pathogen-sensing pathways in obese mice. However, its modulation in human tissues in situations of insulin resistance has not been investigated. The present study was performed to first determine the tissue expression and phosphorylation levels of PKR in the liver, muscle, and adipose tissue in obese humans, and also the modulation of this protein in the adipose tissue of obese patients after bariatric surgery.
Eleven obese subjects who were scheduled to undergo Roux-en-Y Gastric Bypass Procedure participated in this study. Nine apparently healthy lean subjects as a control group were also included.
Our data show that PKR is activated in liver, muscle, and adipose tissue of obese humans and, after bariatric surgery, there is a clear reduction in PKR activation accompanied by a decrease in protein kinase-like endoplasmic reticulum kinase, c-Jun N-terminal kinase, inhibitor of kappa β kinase, and insulin receptor substrate-1 serine 312 phosphorylation in subcutaneous adipose tissue from these patients.
Thus, it is proposed that PKR is an important mediator of obesity-induced insulin resistance and a potential target for the therapy.
双链 RNA 依赖性蛋白激酶（PKR）最近被牵涉到调节肥胖小鼠中营养和病原体感应途径的分子整合。然而，其在胰岛素抵抗情况下的人类组织中的调节尚未被研究。本研究首先旨在确定肥胖人群的肝脏、肌肉和脂肪组织中 PKR 的组织表达和磷酸化水平，并研究肥胖患者在接受减肥手术后脂肪组织中该蛋白的调节。
11 名计划接受 Roux-en-Y 胃旁路手术的肥胖患者参与了本研究。还纳入了 9 名明显健康的瘦对照者作为对照组。
我们的数据表明 PKR 在肥胖人群的肝脏、肌肉和脂肪组织中被激活，并且在减肥手术后，PKR 的激活明显减少，同时伴随着蛋白激酶样内质网激酶、c-Jun N-末端激酶、κB 激酶抑制剂和胰岛素受体底物-1 丝氨酸 312 磷酸化在这些患者的皮下脂肪组织中的减少。
因此，提出 PKR 是肥胖引起的胰岛素抵抗的重要介质，也是治疗的潜在靶点。
