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Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution
Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains p...
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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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010705/ https://www.ncbi.nlm.nih.gov/pubmed/33617872 http://dx.doi.org/10.1016/j.jlr.2021.100049 |
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author | Casey, Carol A. Donohue, Terrence M. Kubik, Jacy L. Kumar, Vikas Naldrett, Michael J. Woods, Nicholas T. Frisbie, Cole P. McNiven, Mark A. Thomes, Paul G. |
author_facet | Casey, Carol A. Donohue, Terrence M. Kubik, Jacy L. Kumar, Vikas Naldrett, Michael J. Woods, Nicholas T. Frisbie, Cole P. McNiven, Mark A. Thomes, Paul G. |
author_sort | Casey, Carol A. |
collection | PubMed |
description | Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol consumption, subsequent abstinence from ethanol, or fasting differentially affects the LD membrane proteome content and that these changes influence how LDs interact with other intracellular organelles. Here, male Wistar rats were pair-fed liquid control or ethanol diets for 6 weeks, and then, randomly chosen animals from both groups were either refed a control diet for 7 days or fasted for 48 h before euthanizing. From all groups, LD membrane proteins from purified liver LDs were analyzed immunochemically and by MS proteomics. Liver LD numbers and sizes were greater in ethanol-fed rats than in pair-fed control, 7-day refed, or fasted rats. Compared with control rats, ethanol feeding markedly altered the LD membrane proteome, enriching LD structural perilipins and proteins involved in lipid biosynthesis, while lowering LD lipase levels. Ethanol feeding also lowered LD-associated mitochondrial and lysosomal proteins. In 7-day refed (i.e., ethanol-abstained) or fasted-ethanol-fed rats, we detected distinct remodeling of the LD proteome, as judged by lower levels of lipid biosynthetic proteins, and enhanced LD interaction with mitochondria and lysosomes. Our study reveals evidence of significant remodeling of the LD membrane proteome that regulates ethanol-induced steatosis, its resolution after withdrawal and abstinence, and changes in LD interactions with other intracellular organelles. |
format | Online Article Text |
id | pubmed-8010705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-80107052021-04-02 Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution Casey, Carol A. Donohue, Terrence M. Kubik, Jacy L. Kumar, Vikas Naldrett, Michael J. Woods, Nicholas T. Frisbie, Cole P. McNiven, Mark A. Thomes, Paul G. J Lipid Res Research Article Lipid droplets (LDs) are composed of neutral lipids enclosed in a phospholipid monolayer, which harbors membrane-associated proteins that regulate LD functions. Despite the crucial role of LDs in lipid metabolism, remodeling of LD protein composition in disease contexts, such as steatosis, remains poorly understood. We hypothesized that chronic ethanol consumption, subsequent abstinence from ethanol, or fasting differentially affects the LD membrane proteome content and that these changes influence how LDs interact with other intracellular organelles. Here, male Wistar rats were pair-fed liquid control or ethanol diets for 6 weeks, and then, randomly chosen animals from both groups were either refed a control diet for 7 days or fasted for 48 h before euthanizing. From all groups, LD membrane proteins from purified liver LDs were analyzed immunochemically and by MS proteomics. Liver LD numbers and sizes were greater in ethanol-fed rats than in pair-fed control, 7-day refed, or fasted rats. Compared with control rats, ethanol feeding markedly altered the LD membrane proteome, enriching LD structural perilipins and proteins involved in lipid biosynthesis, while lowering LD lipase levels. Ethanol feeding also lowered LD-associated mitochondrial and lysosomal proteins. In 7-day refed (i.e., ethanol-abstained) or fasted-ethanol-fed rats, we detected distinct remodeling of the LD proteome, as judged by lower levels of lipid biosynthetic proteins, and enhanced LD interaction with mitochondria and lysosomes. Our study reveals evidence of significant remodeling of the LD membrane proteome that regulates ethanol-induced steatosis, its resolution after withdrawal and abstinence, and changes in LD interactions with other intracellular organelles. American Society for Biochemistry and Molecular Biology 2021-02-20 /pmc/articles/PMC8010705/ /pubmed/33617872 http://dx.doi.org/10.1016/j.jlr.2021.100049 Text en © 2021 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Casey, Carol A. Donohue, Terrence M. Kubik, Jacy L. Kumar, Vikas Naldrett, Michael J. Woods, Nicholas T. Frisbie, Cole P. McNiven, Mark A. Thomes, Paul G. Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution |
title | Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution |
title_full | Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution |
title_fullStr | Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution |
title_full_unstemmed | Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution |
title_short | Lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution |
title_sort | lipid droplet membrane proteome remodeling parallels ethanol-induced hepatic steatosis and its resolution |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010705/ https://www.ncbi.nlm.nih.gov/pubmed/33617872 http://dx.doi.org/10.1016/j.jlr.2021.100049 |
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