Modulation of Double-Stranded RNA-Activated Protein Kinase in Insulin Sensitive Tissues of Obese Humans

Objective: 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. Design and Methods: 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. Results: 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 kinase, and insulin receptor substrate-1 serine 312 phosphorylation in subcutaneous adipose tissue from these patients. Conclusion: Thus, it is proposed that PKR is an important mediator of obesity-induced insulin resistance and a potential target for the therapy.