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Modulation of double-stranded RNA-activated protein kinase in insulin sensitive tissues of obese humans

Bruno M Carvalho1, Alexandre G Oliveira, Mirian Ueno

  • 1Department of Internal Medicine, State University of Campinas, Campinas, SP, Brazil.

Obesity (Silver Spring, Md.)
|March 23, 2013
PubMed
Abstract

Insights

Double-stranded RNA-dependent protein kinase (PKR) is activated in obese humans, contributing to insulin resistance. Bariatric surgery reduces PKR activation, suggesting it as a therapeutic target for obesity-related metabolic dysfunction.

Area of Science:

  • Metabolic disease research
  • Molecular biology
  • Obesity and diabetes research

Background:

  • The double-stranded RNA-dependent protein kinase (PKR) regulates nutrient and pathogen sensing in mice.
  • PKR's role in human insulin resistance, particularly in obesity, remains understudied.
  • Investigating PKR in human tissues is crucial for understanding obesity-related metabolic complications.

Purpose of the Study:

  • To determine the tissue expression and phosphorylation of PKR in obese humans.
  • To assess PKR modulation in adipose tissue following bariatric surgery.
  • To explore PKR's involvement in obesity-induced insulin resistance.

Main Methods:

  • Study included 11 obese subjects undergoing Roux-en-Y Gastric Bypass and 9 lean controls.
  • Tissue samples (liver, muscle, adipose) were analyzed for PKR activation.
  • Phosphorylation levels of key signaling proteins were measured before and after surgery.

Main Results:

  • PKR was found to be activated in the liver, muscle, and adipose tissue of obese individuals.
  • Bariatric surgery led to a significant reduction in PKR activation in subcutaneous adipose tissue.
  • A decrease in phosphorylation of multiple kinases and IRS-1 was observed post-surgery.

Conclusions:

  • PKR is implicated as a key mediator in obesity-associated insulin resistance.
  • Reduced PKR activation post-bariatric surgery suggests its role in metabolic improvement.
  • PKR presents a potential therapeutic target for managing obesity-induced insulin resistance.

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