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Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice

Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had compar...

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Autores principales: Dorochow, Erika, Kraus, Nico, Chenaux-Repond, Nicolas, Pierre, Sandra, Kolbinger, Anja, Geisslinger, Gerd, Ortiz, Cristina, Welsch, Christoph, Trebicka, Jonel, Gurke, Robert, Hahnefeld, Lisa, Klein, Sabine, Scholich, Klaus
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299521/
https://www.ncbi.nlm.nih.gov/pubmed/37373497
http://dx.doi.org/10.3390/ijms241210351
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author Dorochow, Erika
Kraus, Nico
Chenaux-Repond, Nicolas
Pierre, Sandra
Kolbinger, Anja
Geisslinger, Gerd
Ortiz, Cristina
Welsch, Christoph
Trebicka, Jonel
Gurke, Robert
Hahnefeld, Lisa
Klein, Sabine
Scholich, Klaus
author_facet Dorochow, Erika
Kraus, Nico
Chenaux-Repond, Nicolas
Pierre, Sandra
Kolbinger, Anja
Geisslinger, Gerd
Ortiz, Cristina
Welsch, Christoph
Trebicka, Jonel
Gurke, Robert
Hahnefeld, Lisa
Klein, Sabine
Scholich, Klaus
author_sort Dorochow, Erika
collection PubMed
description Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had comparable disease severities regarding mortality rate, neurological behavior, expression of fibrosis marker and albumin levels. Lipid droplet size was higher in NASH than ASH and qualitative differences in the lipidome were mainly based on incorporation of diet-specific fatty acids into triglycerides, phosphatidylcholines and lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels in both models. Here, the corresponding uremic metabolites were only upregulated in NASH suggesting stronger cellular senescence, which was supported by lower antioxidant levels in NASH as compared to ASH. While altered urea cycle metabolites suggest increased nitric oxide synthesis in both models, in ASH, this depended on increased L-homoarginine levels indicating a cardiovascular response mechanism. Interestingly, only in NASH were the levels of tryptophan and its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry showed a decreased macrophage recruitment and an increased polarization towards M2-like macrophages in NASH. In conclusion, with comparable disease severity in both models, higher lipid storage, oxidative stress and tryptophan/kynurenine levels were seen in NASH, leading to distinct immune responses.
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spelling pubmed-102995212023-06-28 Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice Dorochow, Erika Kraus, Nico Chenaux-Repond, Nicolas Pierre, Sandra Kolbinger, Anja Geisslinger, Gerd Ortiz, Cristina Welsch, Christoph Trebicka, Jonel Gurke, Robert Hahnefeld, Lisa Klein, Sabine Scholich, Klaus Int J Mol Sci Article Non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are the leading causes of liver disease worldwide. To identify disease-specific pathomechanisms, we analyzed the lipidome, metabolome and immune cell recruitment in livers in both diseases. Mice harboring ASH or NASH had comparable disease severities regarding mortality rate, neurological behavior, expression of fibrosis marker and albumin levels. Lipid droplet size was higher in NASH than ASH and qualitative differences in the lipidome were mainly based on incorporation of diet-specific fatty acids into triglycerides, phosphatidylcholines and lysophosphatidylcholines. Metabolomic analysis showed downregulated nucleoside levels in both models. Here, the corresponding uremic metabolites were only upregulated in NASH suggesting stronger cellular senescence, which was supported by lower antioxidant levels in NASH as compared to ASH. While altered urea cycle metabolites suggest increased nitric oxide synthesis in both models, in ASH, this depended on increased L-homoarginine levels indicating a cardiovascular response mechanism. Interestingly, only in NASH were the levels of tryptophan and its anti-inflammatory metabolite kynurenine upregulated. Fittingly, high-content immunohistochemistry showed a decreased macrophage recruitment and an increased polarization towards M2-like macrophages in NASH. In conclusion, with comparable disease severity in both models, higher lipid storage, oxidative stress and tryptophan/kynurenine levels were seen in NASH, leading to distinct immune responses. MDPI 2023-06-19 /pmc/articles/PMC10299521/ /pubmed/37373497 http://dx.doi.org/10.3390/ijms241210351 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dorochow, Erika
Kraus, Nico
Chenaux-Repond, Nicolas
Pierre, Sandra
Kolbinger, Anja
Geisslinger, Gerd
Ortiz, Cristina
Welsch, Christoph
Trebicka, Jonel
Gurke, Robert
Hahnefeld, Lisa
Klein, Sabine
Scholich, Klaus
Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice
title Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice
title_full Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice
title_fullStr Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice
title_full_unstemmed Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice
title_short Differential Lipidomics, Metabolomics and Immunological Analysis of Alcoholic and Non-Alcoholic Steatohepatitis in Mice
title_sort differential lipidomics, metabolomics and immunological analysis of alcoholic and non-alcoholic steatohepatitis in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10299521/
https://www.ncbi.nlm.nih.gov/pubmed/37373497
http://dx.doi.org/10.3390/ijms241210351
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