Both genetic predisposition and nutrition factors, such as high sucrose diet (HSD), are involved in the development of metabolic syndrome and insulin resistance. HSD can cause glucose intolerance and liver steatosis and exert hypertriglyceridemic effect. The aim of this study was to investigate the liver transcriptome profile under standard diet or HSD (70 kcal% as sucrose) in two strains of rats. We used Wistar rats and a strain of hereditary hypertriglyceridemic rats (HHTg) as a polygenic model of metabolic syndrome and insulin resistance. HSD feeding in 2 weeks did not affect body weight, but fasting glucose and AUC were increased (P diet<0.01, P strain<0.05). HSD feeding in both strains led to marked accumulation of hepatic triglycerides (P diet<0.01). However, cholesterol concentrations in the liver were reduced after HSD (P diet<0.01) in both strains. Comparative transcriptomic analyses in the liver identified (FDR<0.05) sets of differentially expressed genes in response to HSD common to both strains (n=959 transcripts) as well as HHTg (n=687) and Wistar (n=1531) specific sets. Network analysis revealed overrepresentation of genes involved in transport, synthesis or regulation of lipid metabolism (SREBF, PPARA, PPARG, SCD), mitochondrial dysfunction, excessive oxidative stress response (NRF2-mediated) and endoplasmic reticulum stress. Expression of genes related to sterol biosynthesis and oxidative phosphorylation was down-regulated, whereas genes involved in fatty acid synthesis (FAS, ACC), oxidative or endoplasmic reticulum stress were up-regulated after HSD. Our results support that HSD induced alterations in the liver transcriptome in both strains, which precede the development and progression of liver steatosis. The top regulated gene networks included lipid metabolism and mitochondrial dysfunction. Most of the major expression shifts due to HSD were similar in direction in both strains but differed in magnitude of expression change.


I. Marková: None. M. Hüttl: None. H. Malinska: None. O. Seda: None. L. Kazdova: None.

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