Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice
1
Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbruecke, 14558 Nuthetal, Germany
2
German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany
3
German Center for Cardiovascular Research (DZHK—Partner Site Berlin), 10117 Berlin, Germany
4
Department of Physiological Chemistry, Faculty of Chemistry, University of Vienna, 1090 Vienna, Austria
5
Institute of Nutritional Sciences, University of Potsdam, 14558 Nuthetal, Germany
*
Author to whom correspondence should be addressed.
Academic Editors: Han Moshage, Bresgen Nikolaus and Werner Siems
Antioxidants 2021, 10(4), 501; https://doi.org/10.3390/antiox10040501
Received: 15 February 2021
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Revised: 4 March 2021
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Accepted: 17 March 2021
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Published: 24 March 2021
(This article belongs to the Special Issue Commemorative Issue of Antioxidants Dedicated to Peter Eckl)
Non-alcoholic fatty liver disease (NAFLD), as a consequence of overnutrition caused by high-calorie diets, results in obesity and disturbed lipid homeostasis leading to hepatic lipid droplet formation. Lipid droplets can impair hepatocellular function; therefore, it is of utmost importance to degrade these cellular structures. This requires the normal function of the autophagic-lysosomal system and the ubiquitin-proteasomal system. We demonstrated in NZO mice, a polygenic model of obesity, which were compared to C57BL/6J (B6) mice, that a high-fat diet leads to obesity and accumulation of lipid droplets in the liver. This was accompanied by a loss of autophagy efficiency whereas the activity of lysosomal proteases and the 20S proteasome remained unaffected. The disturbance of cellular protein homeostasis was further demonstrated by the accumulation of 3-nitrotyrosine and 4-hydroxynonenal modified proteins, which are normally prone to degradation. Therefore, we conclude that fat accumulation in the liver due to a high-fat diet is associated with a failure of autophagy and leads to the disturbance of proteostasis. This might further contribute to lipid droplet stabilization and accumulation.
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Keywords:
proteostasis; protein modification; 4-HNE; proteasome; lipid droplets
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MDPI and ACS Style
Korovila, I.; Höhn, A.; Jung, T.; Grune, T.; Ott, C. Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice. Antioxidants 2021, 10, 501. https://doi.org/10.3390/antiox10040501
AMA Style
Korovila I, Höhn A, Jung T, Grune T, Ott C. Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice. Antioxidants. 2021; 10(4):501. https://doi.org/10.3390/antiox10040501
Chicago/Turabian StyleKorovila, Ioanna, Annika Höhn, Tobias Jung, Tilman Grune, and Christiane Ott. 2021. "Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice" Antioxidants 10, no. 4: 501. https://doi.org/10.3390/antiox10040501
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