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

0542626 - FGÚ 2022 RIV CH eng J - Článek v odborném periodiku
Junková, K. - Mirchi, L. F. - Chylíková, B. - Janků, M. - Šilhavý, Jan - Hüttl, M. - Marková, I. - Miklánková, D. - Včelák, J. - Malínská, H. - Pravenec, Michal - Šeda, O. - Liška, František
Hepatic Transcriptome Profiling Reveals Lack of Acsm3 Expression in Polydactylous Rats with High-Fat Diet-Induced Hypertriglyceridemia and Visceral Fat Accumulation.
Nutrients. Roč. 13, č. 5 (2021), č. článku 1462. E-ISSN 2072-6643
Institucionální podpora: RVO:67985823
Klíčová slova: metabolic syndrome * high-fat diet * insulin resistance * hypertriglyceridemia * polydactylous rat * spontaneously hypertensive rat * liver transcriptome * Acsm3
Obor OECD: Endocrinology and metabolism (including diabetes, hormones)
Impakt faktor: 6.706, rok: 2021
Způsob publikování: Open access
https://www.mdpi.com/2072-6643/13/5/1462

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.
Trvalý link: http://hdl.handle.net/11104/0320012