title: PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications.
abstract: 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.
authors.affiliation: Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: G I
authors.initials: GI
authors.lastname: Lancaster
authors.affiliation: Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: H L
authors.initials: HL
authors.lastname: Kammoun
authors.affiliation: Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kraakman
authors.affiliation: Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.|School of Exercise and Nutritional Sciences, Deakin University, Burwood, Victoria 3125, Australia.
authors.forename: G M
authors.initials: GM
authors.lastname: Kowalski
authors.affiliation: Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.|School of Exercise and Nutritional Sciences, Deakin University, Burwood, Victoria 3125, Australia.
authors.forename: C R
authors.initials: CR
authors.lastname: Bruce
authors.affiliation: Cellular and Molecular Metabolism Laboratory, BakerIDI Heart and Diabetes Institute, Melbourne, Victoria 3004, Australia.|Division of Diabetes and Metabolism, Garvan Institute of Medical Research, Darlinghurst, New South Wales 2010, Australia.
authors.forename: M A
authors.initials: MA
authors.lastname: Febbraio
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000818:Animals; D001823:Body Composition; D018845:CD11 Antigens / Q000235:genetics; D017252:CD3 Complex / Q000235:genetics; D002135:Calcium-Binding Proteins; D018932:Chemokine CCL2 / Q000235:genetics; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D005951:Glucose Tolerance Test; D015151:Immunoblotting; D007249:Inflammation / Q000235:genetics* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D039001:Integrin alpha Chains / Q000235:genetics; D007371:Interferon-gamma / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D007962:Leukocytes; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D010168:Palmitates / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics*
chemical_list: C000634132:Adgre1 protein, mouse; D018845:CD11 Antigens; D017252:CD3 Complex; C452842:CD3 antigen, gamma chain; D002135:Calcium-Binding Proteins; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; C587672:IL1B protein, mouse; D007328:Insulin; D039001:Integrin alpha Chains; D053583:Interleukin-1beta; D015850:Interleukin-6; D010168:Palmitates; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C527123:integrin alphaD, mouse; D007371:Interferon-gamma; D019892:eIF-2 Kinase; C000605978:protein kinase R, mouse
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