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

• Main Authors: 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
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Nutrients
• Subjects: metabolic syndrome; high-fat diet; insulin resistance; hypertriglyceridemia; polydactylous rat; spontaneously hypertensive rat
• Online 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 <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.