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

Korovila, Ioanna and Höhn, Annika and Jung, Tobias and Grune, Tilman and Ott, Christiane (2021) Reduced Liver Autophagy in High-Fat Diet Induced Liver Steatosis in New Zealand Obese Mice. Antioxidants, 10 (4). p. 501. ISSN 2076-3921

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Abstract

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.

Item Type: Article
Subjects: STM Digital > Agricultural and Food Science
Depositing User: Unnamed user with email support@stmdigital.org
Date Deposited: 07 Jun 2024 11:00
Last Modified: 07 Jun 2024 11:00
URI: http://research.asianarticleeprint.com/id/eprint/1355

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