An oxidative stress paradox: time for a conceptual change?
Oxidative stress has long been considered a key driving factor of many obesity-related health problems. However, recent work by Merry, Tran et al (Diabetologia DOI 10.1007/s00125-016-4084-3 ) challenges this idea with an interesting study using a hepatocyte-specific Gpx1-knockout (HGKO) mouse. GPX1 is an important detoxification enzyme that converts H2O2to water. The authors found that high-fat diet-fed HGKO mice were more insulin sensitive than wildtype controls, despite elevated hepatic levels of H2O2and evidence of increased systemic oxidative stress. When challenged with a non-alcoholic steatohepatitis (NASH)-inducing diet, HGKO mice were also protected, displaying reduced levels of inflammation and fibrosis with similar levels of steatosis compared with controls. These findings call into question the role of reactive oxygen species in NASH pathogenesis and highlight a potential paradox whereby increased H2O2may be beneficial in some contexts.
Université de Lille, European Genomic Institute for Diabetes (EGID), U1011, Lille, France.|U1011, Inserm, Lille, France.|Department of Biology, Pathology and Genetics, CHU Lille, Lille, France.|U1011, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59000, Lille, France.
Joel T
JT
Haas
Université de Lille, European Genomic Institute for Diabetes (EGID), U1011, Lille, France. bart.staels@pasteur-lille.fr.|U1011, Inserm, Lille, France. bart.staels@pasteur-lille.fr.|Department of Biology, Pathology and Genetics, CHU Lille, Lille, France. bart.staels@pasteur-lille.fr.|U1011, Institut Pasteur de Lille, 1 rue du Professeur Calmette, 59000, Lille, France. bart.staels@pasteur-lille.fr.
Bart
B
Staels
D000818:Animals; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
Glutathione peroxidase; Insulin resistance; Liver; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Oxidative stress; Reactive oxygen species
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