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Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation
Fasting induces lipid accumulation in the liver, while the mechanisms by which fasting dysregulates liver fatty acid oxidation are not clear. Fatty acid ω-oxidation is induced in the fasting state, and administration of dicarboxylic acids to fasting animals decreases plasma ketone bodies. We hypothe...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102918/ https://www.ncbi.nlm.nih.gov/pubmed/33811861 http://dx.doi.org/10.1016/j.jbc.2021.100622 |
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author | Zhang, Xiao Gao, Ting Deng, Senwen Shang, Lin Chen, Xiaocui Chen, Kai Li, Ping Cui, Xiaojuan Zeng, Jia |
author_facet | Zhang, Xiao Gao, Ting Deng, Senwen Shang, Lin Chen, Xiaocui Chen, Kai Li, Ping Cui, Xiaojuan Zeng, Jia |
author_sort | Zhang, Xiao |
collection | PubMed |
description | Fasting induces lipid accumulation in the liver, while the mechanisms by which fasting dysregulates liver fatty acid oxidation are not clear. Fatty acid ω-oxidation is induced in the fasting state, and administration of dicarboxylic acids to fasting animals decreases plasma ketone bodies. We hypothesized that endogenous dicarboxylic acids might play a role in controlling mitochondrial β-oxidation in fasting animals. A peroxisome proliferator-activated receptor-alpha agonist and an inhibitor for peroxisomal β-oxidation were administered to the fasting rats to investigate the role of dicarboxylic acids in liver fatty acid oxidation and lipid homeostasis. We observed that excessive β-oxidation of endogenous dicarboxylic acids by peroxisomes generated considerable levels of succinate in the liver. Excessive succinate oxidation subsequently increased the mitochondrial NADH/NAD(+) ratio and led to an accumulation of 3-OH-CoA and 2-enoyl-CoA intermediates in the liver. This further induced feedback suppression of mitochondrial β-oxidation and promoted hepatic lipid deposition and steatosis. Specific inhibition of peroxisomal β-oxidation attenuated fasting-induced lipid deposition in the liver by reducing succinate production and enhancing mitochondrial fatty acid oxidation. We conclude that suppression of mitochondrial β-oxidation by oxidation of dicarboxylic acids serves as a mechanism for fasting-induced hepatic lipid accumulation and identifies cross talk between peroxisomal and mitochondrial fatty acid oxidation. |
format | Online Article Text |
id | pubmed-8102918 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-81029182021-05-14 Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation Zhang, Xiao Gao, Ting Deng, Senwen Shang, Lin Chen, Xiaocui Chen, Kai Li, Ping Cui, Xiaojuan Zeng, Jia J Biol Chem Research Article Fasting induces lipid accumulation in the liver, while the mechanisms by which fasting dysregulates liver fatty acid oxidation are not clear. Fatty acid ω-oxidation is induced in the fasting state, and administration of dicarboxylic acids to fasting animals decreases plasma ketone bodies. We hypothesized that endogenous dicarboxylic acids might play a role in controlling mitochondrial β-oxidation in fasting animals. A peroxisome proliferator-activated receptor-alpha agonist and an inhibitor for peroxisomal β-oxidation were administered to the fasting rats to investigate the role of dicarboxylic acids in liver fatty acid oxidation and lipid homeostasis. We observed that excessive β-oxidation of endogenous dicarboxylic acids by peroxisomes generated considerable levels of succinate in the liver. Excessive succinate oxidation subsequently increased the mitochondrial NADH/NAD(+) ratio and led to an accumulation of 3-OH-CoA and 2-enoyl-CoA intermediates in the liver. This further induced feedback suppression of mitochondrial β-oxidation and promoted hepatic lipid deposition and steatosis. Specific inhibition of peroxisomal β-oxidation attenuated fasting-induced lipid deposition in the liver by reducing succinate production and enhancing mitochondrial fatty acid oxidation. We conclude that suppression of mitochondrial β-oxidation by oxidation of dicarboxylic acids serves as a mechanism for fasting-induced hepatic lipid accumulation and identifies cross talk between peroxisomal and mitochondrial fatty acid oxidation. American Society for Biochemistry and Molecular Biology 2021-03-31 /pmc/articles/PMC8102918/ /pubmed/33811861 http://dx.doi.org/10.1016/j.jbc.2021.100622 Text en © 2021 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Article Zhang, Xiao Gao, Ting Deng, Senwen Shang, Lin Chen, Xiaocui Chen, Kai Li, Ping Cui, Xiaojuan Zeng, Jia Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation |
title | Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation |
title_full | Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation |
title_fullStr | Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation |
title_full_unstemmed | Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation |
title_short | Fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation |
title_sort | fasting induces hepatic lipid accumulation by stimulating peroxisomal dicarboxylic acid oxidation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102918/ https://www.ncbi.nlm.nih.gov/pubmed/33811861 http://dx.doi.org/10.1016/j.jbc.2021.100622 |
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