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Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor

Obesity is often associated with dyslipidemia and hepatosteatosis. A number of animal models of non-alcoholic fatty liver disease (NAFLD) are established but they significantly differ in the molecular and biochemical changes depending on the genetic modification and diet used. Mice deficient for mel...

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Autores principales: Lede, Vera, Meusel, Andrej, Garten, Antje, Popkova, Yulia, Penke, Melanie, Franke, Christin, Ricken, Albert, Schulz, Angela, Kiess, Wieland, Huster, Daniel, Schöneberg, Torsten, Schiller, Jürgen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313158/
https://www.ncbi.nlm.nih.gov/pubmed/28207798
http://dx.doi.org/10.1371/journal.pone.0172000
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author Lede, Vera
Meusel, Andrej
Garten, Antje
Popkova, Yulia
Penke, Melanie
Franke, Christin
Ricken, Albert
Schulz, Angela
Kiess, Wieland
Huster, Daniel
Schöneberg, Torsten
Schiller, Jürgen
author_facet Lede, Vera
Meusel, Andrej
Garten, Antje
Popkova, Yulia
Penke, Melanie
Franke, Christin
Ricken, Albert
Schulz, Angela
Kiess, Wieland
Huster, Daniel
Schöneberg, Torsten
Schiller, Jürgen
author_sort Lede, Vera
collection PubMed
description Obesity is often associated with dyslipidemia and hepatosteatosis. A number of animal models of non-alcoholic fatty liver disease (NAFLD) are established but they significantly differ in the molecular and biochemical changes depending on the genetic modification and diet used. Mice deficient for melanocortin type 4 receptor (Mc4r(mut)) develop hyperphagia, obesity, and subsequently NAFLD already under regular chow and resemble more closely the energy supply-driven obesity found in humans. This animal model was used to assess the molecular and biochemical consequences of hyperphagia-induced obesity on hepatic lipid metabolism. We analyzed transcriptome changes in Mc4r(mut) mice by RNA sequencing and used high resolution (1)H magic angle spinning NMR spectroscopy and MALDI-TOF mass spectrometry to assess changes in the lipid composition. On the transcriptomic level we found significant changes in components of the triacylglycerol metabolism, unsaturated fatty acids biosynthesis, peroxisome proliferator-activated receptor signaling pathways, and lipid transport and storage compared to the wild-type. These findings were supported by increases in triacylglycerol, monounsaturated fatty acid, and arachidonic acid levels. The transcriptome signatures significantly differ from those of other NAFLD mouse models supporting the concept of hepatic subphenotypes depending on the genetic background and diet. Comparative analyses of our data with previous studies allowed for the identification of common changes and genotype-specific components and pathways involved in obesity-associated NAFLD.
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spelling pubmed-53131582017-03-03 Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor Lede, Vera Meusel, Andrej Garten, Antje Popkova, Yulia Penke, Melanie Franke, Christin Ricken, Albert Schulz, Angela Kiess, Wieland Huster, Daniel Schöneberg, Torsten Schiller, Jürgen PLoS One Research Article Obesity is often associated with dyslipidemia and hepatosteatosis. A number of animal models of non-alcoholic fatty liver disease (NAFLD) are established but they significantly differ in the molecular and biochemical changes depending on the genetic modification and diet used. Mice deficient for melanocortin type 4 receptor (Mc4r(mut)) develop hyperphagia, obesity, and subsequently NAFLD already under regular chow and resemble more closely the energy supply-driven obesity found in humans. This animal model was used to assess the molecular and biochemical consequences of hyperphagia-induced obesity on hepatic lipid metabolism. We analyzed transcriptome changes in Mc4r(mut) mice by RNA sequencing and used high resolution (1)H magic angle spinning NMR spectroscopy and MALDI-TOF mass spectrometry to assess changes in the lipid composition. On the transcriptomic level we found significant changes in components of the triacylglycerol metabolism, unsaturated fatty acids biosynthesis, peroxisome proliferator-activated receptor signaling pathways, and lipid transport and storage compared to the wild-type. These findings were supported by increases in triacylglycerol, monounsaturated fatty acid, and arachidonic acid levels. The transcriptome signatures significantly differ from those of other NAFLD mouse models supporting the concept of hepatic subphenotypes depending on the genetic background and diet. Comparative analyses of our data with previous studies allowed for the identification of common changes and genotype-specific components and pathways involved in obesity-associated NAFLD. Public Library of Science 2017-02-16 /pmc/articles/PMC5313158/ /pubmed/28207798 http://dx.doi.org/10.1371/journal.pone.0172000 Text en © 2017 Lede et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lede, Vera
Meusel, Andrej
Garten, Antje
Popkova, Yulia
Penke, Melanie
Franke, Christin
Ricken, Albert
Schulz, Angela
Kiess, Wieland
Huster, Daniel
Schöneberg, Torsten
Schiller, Jürgen
Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor
title Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor
title_full Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor
title_fullStr Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor
title_full_unstemmed Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor
title_short Altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor
title_sort altered hepatic lipid metabolism in mice lacking both the melanocortin type 4 receptor and low density lipoprotein receptor
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5313158/
https://www.ncbi.nlm.nih.gov/pubmed/28207798
http://dx.doi.org/10.1371/journal.pone.0172000
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