Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin

Abstract Alzheimer’s disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-prod...

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Autores principales:	Anna A. Lauer, Daniel Janitschke, Malena dos Santos Guilherme, Vu Thu Thuy Nguyen, Cornel M. Bachmann, Sen Qiao, Bianca Schrul, Ulrich Boehm, Heike S. Grimm, Tobias Hartmann, Kristina Endres, Marcus O. W. Grimm
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5639c0b6d26b424195703800c12d0d3c
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spelling	oai:doaj.org-article:5639c0b6d26b424195703800c12d0d3c2021-12-02T16:06:41ZShotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin10.1038/s41598-021-94706-32045-2322https://doaj.org/article/5639c0b6d26b424195703800c12d0d3c2021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94706-3https://doaj.org/toc/2045-2322Abstract Alzheimer’s disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-production and elicits cognitive improvement in AD mouse models. As an unintended side effect, acitretin could result in hyperlipidemia. Here, we analyzed the impact of acitretin on the lipidome in brain and liver tissue in the 5xFAD mouse-model. In line with literature, triglycerides were increased in liver accompanied by increased PCaa, plasmalogens and acyl-carnitines, whereas SM-species were decreased. In brain, these effects were partially enhanced or similar but also inverted. While for SM and plasmalogens similar effects were found, PCaa, TAG and acyl-carnitines showed an inverse effect in both tissues. Our findings emphasize, that potential pharmaceuticals to treat AD should be carefully monitored with respect to lipid-homeostasis because APP-processing itself modulates lipid-metabolism and medication might result in further and unexpected changes. Moreover, deducing effects of brain lipid-homeostasis from results obtained for other tissues should be considered cautiously. With respect to acitretin, the increase in brain plasmalogens might display a further positive probability in AD-treatment, while other results, such as decreased SM, indicate the need of medical surveillance for treated patients.Anna A. LauerDaniel JanitschkeMalena dos Santos GuilhermeVu Thu Thuy NguyenCornel M. BachmannSen QiaoBianca SchrulUlrich BoehmHeike S. GrimmTobias HartmannKristina EndresMarcus O. W. GrimmNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Anna A. Lauer Daniel Janitschke Malena dos Santos Guilherme Vu Thu Thuy Nguyen Cornel M. Bachmann Sen Qiao Bianca Schrul Ulrich Boehm Heike S. Grimm Tobias Hartmann Kristina Endres Marcus O. W. Grimm Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin
description	Abstract Alzheimer’s disease (AD) is a very frequent neurodegenerative disorder characterized by an accumulation of amyloid-β (Aβ). Acitretin, a retinoid-derivative and approved treatment for Psoriasis vulgaris, increases non-amyloidogenic Amyloid-Precursor-Protein-(APP)-processing, prevents Aβ-production and elicits cognitive improvement in AD mouse models. As an unintended side effect, acitretin could result in hyperlipidemia. Here, we analyzed the impact of acitretin on the lipidome in brain and liver tissue in the 5xFAD mouse-model. In line with literature, triglycerides were increased in liver accompanied by increased PCaa, plasmalogens and acyl-carnitines, whereas SM-species were decreased. In brain, these effects were partially enhanced or similar but also inverted. While for SM and plasmalogens similar effects were found, PCaa, TAG and acyl-carnitines showed an inverse effect in both tissues. Our findings emphasize, that potential pharmaceuticals to treat AD should be carefully monitored with respect to lipid-homeostasis because APP-processing itself modulates lipid-metabolism and medication might result in further and unexpected changes. Moreover, deducing effects of brain lipid-homeostasis from results obtained for other tissues should be considered cautiously. With respect to acitretin, the increase in brain plasmalogens might display a further positive probability in AD-treatment, while other results, such as decreased SM, indicate the need of medical surveillance for treated patients.
format	article
author	Anna A. Lauer Daniel Janitschke Malena dos Santos Guilherme Vu Thu Thuy Nguyen Cornel M. Bachmann Sen Qiao Bianca Schrul Ulrich Boehm Heike S. Grimm Tobias Hartmann Kristina Endres Marcus O. W. Grimm
author_facet	Anna A. Lauer Daniel Janitschke Malena dos Santos Guilherme Vu Thu Thuy Nguyen Cornel M. Bachmann Sen Qiao Bianca Schrul Ulrich Boehm Heike S. Grimm Tobias Hartmann Kristina Endres Marcus O. W. Grimm
author_sort	Anna A. Lauer
title	Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin
title_short	Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin
title_full	Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin
title_fullStr	Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin
title_full_unstemmed	Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin
title_sort	shotgun lipidomics of liver and brain tissue of alzheimer’s disease model mice treated with acitretin
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/5639c0b6d26b424195703800c12d0d3c
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Shotgun lipidomics of liver and brain tissue of Alzheimer’s disease model mice treated with acitretin

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