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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Biochemistry and Molecular Biology 2021
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.
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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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