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Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation

Metabolic syndrome (MetS) is an important cause of worldwide morbidity and mortality. Its complex pathogenesis includes, on the one hand, sedentary lifestyle and high caloric intake, and, on the other hand, there is a clear genetic predisposition. PD (Polydactylous rat) is an animal model of hypertr...

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Autores principales: Junková, Kristýna, Mirchi, Lukáš F., Chylíková, Blanka, Janků, Michaela, Šilhavý, Jan, Hüttl, Martina, Marková, Irena, Miklánková, Denisa, Včelák, Josef, Malínská, Hana, Pravenec, Michal, Šeda, Ondřej, Liška, František
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147112/
https://www.ncbi.nlm.nih.gov/pubmed/33923085
http://dx.doi.org/10.3390/nu13051462
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author Junková, Kristýna
Mirchi, Lukáš F.
Chylíková, Blanka
Janků, Michaela
Šilhavý, Jan
Hüttl, Martina
Marková, Irena
Miklánková, Denisa
Včelák, Josef
Malínská, Hana
Pravenec, Michal
Šeda, Ondřej
Liška, František
author_facet Junková, Kristýna
Mirchi, Lukáš F.
Chylíková, Blanka
Janků, Michaela
Šilhavý, Jan
Hüttl, Martina
Marková, Irena
Miklánková, Denisa
Včelák, Josef
Malínská, Hana
Pravenec, Michal
Šeda, Ondřej
Liška, František
author_sort Junková, Kristýna
collection PubMed
description Metabolic syndrome (MetS) is an important cause of worldwide morbidity and mortality. Its complex pathogenesis includes, on the one hand, sedentary lifestyle and high caloric intake, and, on the other hand, there is a clear genetic predisposition. PD (Polydactylous rat) is an animal model of hypertriglyceridemia, insulin resistance, and obesity. To unravel the genetic and pathophysiologic background of this phenotype, we compared morphometric and metabolic parameters as well as liver transcriptomes among PD, spontaneously hypertensive rat, and Brown Norway (BN) strains fed a high-fat diet (HFD). After 4 weeks of HFD, PD rats displayed marked hypertriglyceridemia but without the expected hepatic steatosis. Moreover, the PD strain showed significant weight gain, including increased weight of retroperitoneal and epididymal fat pads, and impaired glucose tolerance. In the liver transcriptome, we found 5480 differentially expressed genes, which were enriched for pathways involved in fatty acid beta and omega oxidation, glucocorticoid metabolism, oxidative stress, complement activation, triacylglycerol and lipid droplets synthesis, focal adhesion, prostaglandin synthesis, interferon signaling, and tricarboxylic acid cycle pathways. Interestingly, the PD strain, contrary to SHR and BN rats, did not express the Acsm3 (acyl-CoA synthetase medium-chain family member 3) gene in the liver. Together, these results suggest disturbances in fatty acid utilization as a molecular mechanism predisposing PD rats to hypertriglyceridemia and fat accumulation.
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spelling pubmed-81471122021-05-26 Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation Junková, Kristýna Mirchi, Lukáš F. Chylíková, Blanka Janků, Michaela Šilhavý, Jan Hüttl, Martina Marková, Irena Miklánková, Denisa Včelák, Josef Malínská, Hana Pravenec, Michal Šeda, Ondřej Liška, František Nutrients Article Metabolic syndrome (MetS) is an important cause of worldwide morbidity and mortality. Its complex pathogenesis includes, on the one hand, sedentary lifestyle and high caloric intake, and, on the other hand, there is a clear genetic predisposition. PD (Polydactylous rat) is an animal model of hypertriglyceridemia, insulin resistance, and obesity. To unravel the genetic and pathophysiologic background of this phenotype, we compared morphometric and metabolic parameters as well as liver transcriptomes among PD, spontaneously hypertensive rat, and Brown Norway (BN) strains fed a high-fat diet (HFD). After 4 weeks of HFD, PD rats displayed marked hypertriglyceridemia but without the expected hepatic steatosis. Moreover, the PD strain showed significant weight gain, including increased weight of retroperitoneal and epididymal fat pads, and impaired glucose tolerance. In the liver transcriptome, we found 5480 differentially expressed genes, which were enriched for pathways involved in fatty acid beta and omega oxidation, glucocorticoid metabolism, oxidative stress, complement activation, triacylglycerol and lipid droplets synthesis, focal adhesion, prostaglandin synthesis, interferon signaling, and tricarboxylic acid cycle pathways. Interestingly, the PD strain, contrary to SHR and BN rats, did not express the Acsm3 (acyl-CoA synthetase medium-chain family member 3) gene in the liver. Together, these results suggest disturbances in fatty acid utilization as a molecular mechanism predisposing PD rats to hypertriglyceridemia and fat accumulation. MDPI 2021-04-25 /pmc/articles/PMC8147112/ /pubmed/33923085 http://dx.doi.org/10.3390/nu13051462 Text en © 2021 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
Junková, Kristýna
Mirchi, Lukáš F.
Chylíková, Blanka
Janků, Michaela
Šilhavý, Jan
Hüttl, Martina
Marková, Irena
Miklánková, Denisa
Včelák, Josef
Malínská, Hana
Pravenec, Michal
Šeda, Ondřej
Liška, František
Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation
title Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation
title_full Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation
title_fullStr Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation
title_full_unstemmed Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation
title_short Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation
title_sort hepatic transcriptome profiling reveals lack of acsm3 expression in polydactylous rats with high-fat diet-induced hypertriglyceridemia and visceral fat accumulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147112/
https://www.ncbi.nlm.nih.gov/pubmed/33923085
http://dx.doi.org/10.3390/nu13051462
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