Alterations of Lipid Profile in Livers with Impaired Lipophagy

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Various mechanisms such as an increased uptake in fatty acids or de novo synthesis contribute to the development of steatosis and progression to more severe stages. Furthermore, it has been shown...

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Main Authors: Wenke Jonas, Kristin Schwerbel, Lisa Zellner, Markus Jähnert, Pascal Gottmann, Annette Schürmann
Format: Article
Language:English
Published: MDPI AG 2022-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/19/11863
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author Wenke Jonas
Kristin Schwerbel
Lisa Zellner
Markus Jähnert
Pascal Gottmann
Annette Schürmann
author_facet Wenke Jonas
Kristin Schwerbel
Lisa Zellner
Markus Jähnert
Pascal Gottmann
Annette Schürmann
author_sort Wenke Jonas
collection DOAJ
description Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Various mechanisms such as an increased uptake in fatty acids or de novo synthesis contribute to the development of steatosis and progression to more severe stages. Furthermore, it has been shown that impaired lipophagy, the degradation of lipids by autophagic processes, contributes to NAFLD. Through an unbiased lipidome analysis of mouse livers in a genetic model of impaired lipophagy, we aimed to determine the resulting alterations in the lipidome. Observed changes overlap with those of the human disease. Overall, the entire lipid content and in particular the triacylglycerol concentration increased under conditions of impaired lipophagy. In addition, we detected a reduction in long-chain polyunsaturated fatty acids (PUFAs) and an increased ratio of n-6 PUFAs to n-3 PUFAs, which was due to the depletion of n-3 PUFAs. Although the abundance of major phospholipid classes was reduced, the ratio of phosphatidylcholines to phosphatidylethanolamines was not affected. In conclusion, this study demonstrates that impaired lipophagy contributes to the pathology of NAFLD and is associated with an altered lipid profile. However, the lipid pattern does not appear to be specific for lipophagic alterations, as it resembles mainly that described in relation to fatty liver disease.
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spelling doaj.art-3bb9c4df8f3d4349a59e3db16816a5052023-11-23T20:40:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-10-0123191186310.3390/ijms231911863Alterations of Lipid Profile in Livers with Impaired LipophagyWenke Jonas0Kristin Schwerbel1Lisa Zellner2Markus Jähnert3Pascal Gottmann4Annette Schürmann5Department of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, GermanyDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, GermanyDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, GermanyDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, GermanyDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, GermanyDepartment of Experimental Diabetology, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, GermanyNon-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Various mechanisms such as an increased uptake in fatty acids or de novo synthesis contribute to the development of steatosis and progression to more severe stages. Furthermore, it has been shown that impaired lipophagy, the degradation of lipids by autophagic processes, contributes to NAFLD. Through an unbiased lipidome analysis of mouse livers in a genetic model of impaired lipophagy, we aimed to determine the resulting alterations in the lipidome. Observed changes overlap with those of the human disease. Overall, the entire lipid content and in particular the triacylglycerol concentration increased under conditions of impaired lipophagy. In addition, we detected a reduction in long-chain polyunsaturated fatty acids (PUFAs) and an increased ratio of n-6 PUFAs to n-3 PUFAs, which was due to the depletion of n-3 PUFAs. Although the abundance of major phospholipid classes was reduced, the ratio of phosphatidylcholines to phosphatidylethanolamines was not affected. In conclusion, this study demonstrates that impaired lipophagy contributes to the pathology of NAFLD and is associated with an altered lipid profile. However, the lipid pattern does not appear to be specific for lipophagic alterations, as it resembles mainly that described in relation to fatty liver disease.https://www.mdpi.com/1422-0067/23/19/11863non-alcoholic fatty liver diseaselipophagylipidomicsfatty acid profilelong-chain polyunsaturated fatty acids
spellingShingle Wenke Jonas
Kristin Schwerbel
Lisa Zellner
Markus Jähnert
Pascal Gottmann
Annette Schürmann
Alterations of Lipid Profile in Livers with Impaired Lipophagy
International Journal of Molecular Sciences
non-alcoholic fatty liver disease
lipophagy
lipidomics
fatty acid profile
long-chain polyunsaturated fatty acids
title Alterations of Lipid Profile in Livers with Impaired Lipophagy
title_full Alterations of Lipid Profile in Livers with Impaired Lipophagy
title_fullStr Alterations of Lipid Profile in Livers with Impaired Lipophagy
title_full_unstemmed Alterations of Lipid Profile in Livers with Impaired Lipophagy
title_short Alterations of Lipid Profile in Livers with Impaired Lipophagy
title_sort alterations of lipid profile in livers with impaired lipophagy
topic non-alcoholic fatty liver disease
lipophagy
lipidomics
fatty acid profile
long-chain polyunsaturated fatty acids
url https://www.mdpi.com/1422-0067/23/19/11863
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AT lisazellner alterationsoflipidprofileinliverswithimpairedlipophagy
AT markusjahnert alterationsoflipidprofileinliverswithimpairedlipophagy
AT pascalgottmann alterationsoflipidprofileinliverswithimpairedlipophagy
AT annetteschurmann alterationsoflipidprofileinliverswithimpairedlipophagy