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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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8147112 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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