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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8063826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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