Open AccessPKR modulates abnormal brain signaling in experimental obesity
Author(s) -
Mariko Taga,
François Mouton-Liger,
Malha Sadoune,
Sarah Gourmaud,
Jenny Norman,
Marion Tible,
Sylvie Thomasseau,
Claire Paquet,
James A. R. Nicoll,
Delphine Boche,
Jacques Hugon
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0196983
Subject(s) - protein kinase r , endocrinology , medicine , inflammation , type 2 diabetes , diabetes mellitus , neurodegeneration , inflammasome , biology , insulin , insulin resistance , protein kinase a , kinase , disease , microbiology and biotechnology , mitogen activated protein kinase kinase
Metabolic disorders including obesity and type 2 diabetes are known to be associated with chronic inflammation and are obvious risk factors for Alzheimer’s disease. Recent evidences concerning obesity and diabetes suggest that the metabolic inflammasome (“metaflammasome”) mediates chronic inflammation. The double-stranded RNA-dependent protein kinase (PKR) is a central component of the metaflammasome. In wild type (WT) and PKR -/- mice, blood glucose, insulin and lipid levels and the brain expression of the phosphorylated components of the metaflammasome—PKR, JNK, IRS1 and IKKbeta—were studied after the induction of obesity by a high fat diet (HFD). The results showed significant increased levels of activated brain metaflammasome proteins in exposed WT mice but the changes were not significant in PKR -/- mice. In addition, gain weight was observed in WT mice and also in PKR -/- mice exposed to HFD. Increased blood insulin level was more accentuated in PKR -/- mice. The modulation of PKR activity could be an appropriate therapeutic approach, aimed at reducing abnormal brain metabolism and inflammation linked to metabolic disorders in order to reduce the risk of neurodegeneration.