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

Nature Communications
Graeme I LancasterMark A Febbraio

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.

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Citations

Apr 1, 2017·The Journal of Endocrinology·Greg M KowalskiClinton R Bruce
Apr 7, 2016·Journal of Lipid Research·Petra HirsovaHarmeet Malhi
Feb 10, 2017·Nature·Gökhan S Hotamisligil
Jul 21, 2017·Expert Reviews in Molecular Medicine·M B Garcia-OrtegaM A Garcia
Feb 20, 2016·Nature Reviews. Endocrinology·Claire Greenhill
Oct 28, 2019·The Journal of Clinical Endocrinology and Metabolism·Yue QiZhengping Yi
May 26, 2018·PloS One·Mariko TagaJacques Hugon
Sep 5, 2019·Frontiers in Cardiovascular Medicine·Esam S B SalemTakahisa Nakamura
May 31, 2019·Journal of Cellular and Molecular Medicine·Chiakang HoQingfeng Li
Jan 29, 2019·Frontiers in Molecular Neuroscience·Shunit Gal-Ben-AriKobi Rosenblum
Jan 3, 2021·The FEBS Journal·Evelyn ChukwurahMaria Hatzoglou
Jan 24, 2021·Molecular Metabolism·Imke L LemmerAlexander Bartelt
Jul 28, 2020·Molecular Metabolism·Lauren Y SandemanChristopher G Proud
Jun 27, 2021·The International Journal of Biochemistry & Cell Biology·Benedicth UkhueduanRekha C Patel

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Methods Mentioned

BETA
flow cytometry
ELISA
dissection
FACS

Software Mentioned

FACS Diva
SPSS Statistics
FlowJo

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