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Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice

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 degrad...

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Autores principales: Korovila, Ioanna, Höhn, Annika, Jung, Tobias, Grune, Tilman, Ott, Christiane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063826/
https://www.ncbi.nlm.nih.gov/pubmed/33804819
http://dx.doi.org/10.3390/antiox10040501
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author Korovila, Ioanna
Höhn, Annika
Jung, Tobias
Grune, Tilman
Ott, Christiane
author_facet Korovila, Ioanna
Höhn, Annika
Jung, Tobias
Grune, Tilman
Ott, Christiane
author_sort Korovila, Ioanna
collection PubMed
description 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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spelling pubmed-80638262021-04-24 Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice Korovila, Ioanna Höhn, Annika Jung, Tobias Grune, Tilman Ott, Christiane Antioxidants (Basel) Article 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. MDPI 2021-03-24 /pmc/articles/PMC8063826/ /pubmed/33804819 http://dx.doi.org/10.3390/antiox10040501 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ).
spellingShingle Article
Korovila, Ioanna
Höhn, Annika
Jung, Tobias
Grune, Tilman
Ott, Christiane
Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice
title Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice
title_full Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice
title_fullStr Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice
title_full_unstemmed Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice
title_short Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice
title_sort reduced liver autophagy in high-fat diet induced liver steatosis in new zealand obese mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8063826/
https://www.ncbi.nlm.nih.gov/pubmed/33804819
http://dx.doi.org/10.3390/antiox10040501
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