PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications

• Published in: Nature communications Vol. 7; no. 1; p. 10626
• Main Authors: Lancaster, G I, Kammoun, H L, Kraakman, M J, Kowalski, G M, Bruce, C R, Febbraio, M A
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 03.02.2016; Nature Portfolio
• Subjects: Adipose Tissue, White - metabolism; Animals; Body Composition; CD11 Antigens - genetics; CD3 Complex - genetics; Chemokine CCL2 - genetics; Diet, High-Fat; Disease Models, Animal; eIF-2 Kinase - genetics; Fatty Liver - genetics; Fatty Liver - metabolism; Fatty Liver - pathology; Flow Cytometry; Gene Expression Profiling; Glucose Tolerance Test; Immunoblotting; Inflammation - genetics; Inflammation - metabolism; Insulin - blood; Integrin alpha Chains - genetics; Interferon-gamma - genetics; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Interleukin-6 - genetics; Leukocytes; Liver - metabolism; Liver - pathology; Macrophages - drug effects; Macrophages - metabolism; Mice; Mice, Knockout; Obesity - genetics; Obesity - metabolism; Palmitates - pharmacology; Receptors, Cell Surface - genetics; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - metabolism; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms10626

Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro. Here we show that the deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. Treatment with the saturated fatty acid palmitate in vitro induced comparable levels of inflammation in WT and PKR KO macrophages, demonstrating that PKR is not necessary for the sensing of pro-inflammatory lipids. These results challenge the proposed role for PKR in obesity, its associated metabolic complications and its role in lipid-induced inflammation.