Hepatic Transcriptome Profiling Reveals Lack of <i>Acsm3</i> 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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MDPI AG
2021-04-01
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| Online Access: | https://www.mdpi.com/2072-6643/13/5/1462 |
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| author | Kristýna Junková Lukáš F. Mirchi Blanka Chylíková Michaela Janků Jan Šilhavý Martina Hüttl Irena Marková Denisa Miklánková Josef Včelák Hana Malínská Michal Pravenec Ondřej Šeda František Liška |
| author_facet | Kristýna Junková Lukáš F. Mirchi Blanka Chylíková Michaela Janků Jan Šilhavý Martina Hüttl Irena Marková Denisa Miklánková Josef Včelák Hana Malínská Michal Pravenec Ondřej Šeda František Liška |
| author_sort | Kristýna Junková |
| collection | DOAJ |
| 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 <i>Acsm3</i> (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. |
| first_indexed | 2024-03-10T11:58:32Z |
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| id | doaj.art-062480d685f247a1913c1ce07c44f10d |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T11:58:32Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-062480d685f247a1913c1ce07c44f10d2023-11-21T17:07:04ZengMDPI AGNutrients2072-66432021-04-01135146210.3390/nu13051462Hepatic Transcriptome Profiling Reveals Lack of <i>Acsm3</i> Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat AccumulationKristýna Junková0Lukáš F. Mirchi1Blanka Chylíková2Michaela Janků3Jan Šilhavý4Martina Hüttl5Irena Marková6Denisa Miklánková7Josef Včelák8Hana Malínská9Michal Pravenec10Ondřej Šeda11František Liška12Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech RepublicDepartment of Genetics of Model Diseases, Institute of Physiology, Czech Academy of Sciences, 142 20 Prague, Czech RepublicInstitute for Clinical and Experimental Medicine, 140 21 Prague, Czech RepublicInstitute for Clinical and Experimental Medicine, 140 21 Prague, Czech RepublicInstitute for Clinical and Experimental Medicine, 140 21 Prague, Czech RepublicInstitute of Endocrinology, 116 94 Prague, Czech RepublicInstitute for Clinical and Experimental Medicine, 140 21 Prague, Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech RepublicInstitute of Biology and Medical Genetics, First Faculty of Medicine, Charles University and General University Hospital, 128 00 Prague, Czech RepublicMetabolic 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 <i>Acsm3</i> (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.https://www.mdpi.com/2072-6643/13/5/1462metabolic syndromehigh-fat dietinsulin resistancehypertriglyceridemiapolydactylous ratspontaneously hypertensive rat |
| spellingShingle | Kristýna Junková Lukáš F. Mirchi Blanka Chylíková Michaela Janků Jan Šilhavý Martina Hüttl Irena Marková Denisa Miklánková Josef Včelák Hana Malínská Michal Pravenec Ondřej Šeda František Liška Hepatic Transcriptome Profiling Reveals Lack of <i>Acsm3</i> Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation Nutrients metabolic syndrome high-fat diet insulin resistance hypertriglyceridemia polydactylous rat spontaneously hypertensive rat |
| title | Hepatic Transcriptome Profiling Reveals Lack of <i>Acsm3</i> Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation |
| title_full | Hepatic Transcriptome Profiling Reveals Lack of <i>Acsm3</i> Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation |
| title_fullStr | Hepatic Transcriptome Profiling Reveals Lack of <i>Acsm3</i> Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation |
| title_full_unstemmed | Hepatic Transcriptome Profiling Reveals Lack of <i>Acsm3</i> Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation |
| title_short | Hepatic Transcriptome Profiling Reveals Lack of <i>Acsm3</i> Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation |
| title_sort | hepatic transcriptome profiling reveals lack of i acsm3 i expression in polydactylous rats with high fat diet induced hypertriglyceridemia and visceral fat accumulation |
| topic | metabolic syndrome high-fat diet insulin resistance hypertriglyceridemia polydactylous rat spontaneously hypertensive rat |
| url | https://www.mdpi.com/2072-6643/13/5/1462 |
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