The development and progression of insulin resistance is driven by genetic and enviromental factors and their interactions. Sucrose belongs to nutrition factors with lipogenic impact, induces de novo lipogenesis, reduces fatty acid oxidation and can deteriorate insulin sensitivity. The aim of study was to investigate transcriptome profile in adipose and muscle tissues under standard or high sucrose diet (HSD) (70 kcal% as sucrose) in two strains of rats - Wistar and a strain of hereditary hypertriglyceridemic rats (HHTg) as a polygenic model of metabolic syndrome and insulin resistance. The transcriptome analysis was evaluated in the context of development and progression of insulin resistance. HSD feeding in 2 weeks increased epididymal adipose tissue (EAT) weight in both strains (P diet<0.05), but not body weight. In addition, HSD feeding resulted in elevated levels of fasting glucose (P diet<0.05), insulin (P diet<0.01) and FFA (P diet<0.05, P strain<0.05), but adiponectin was decreased only in HHTg rats (P<0.01). Insulin sensitivity of EAT was significantly reduced (P diet<0.05, P strain<0.05), but HSD did not change triglycerides or insulin sensitivity in muscle. In skeletal muscle, HSD significantly changed expression (FDR<0.05) of 20 transcripts in HHTg and 21 in Wistar (only 2 common). In EAT, HSD significantly changed expression of 810 transcripts in HHTG and 1823 in Wistar (344 common). The most affected pathways were insulin receptor signaling in HHTg and mitochondrial dysfunction and oxidative phosphorylation in Wistar rats. Major regulator nodes of the mechanistic networks included insulin, SCD and miR-27 for HSD effect in HHTg and LIPE, miR-27 and VEGF in Wistar strain.

In conclusion, HSD feeding impaired insulin sensitivity in both rat strains. Transcriptomic alterations in adipose tissue precede muscle changes caused by HSD and show distinct patterns in genetically susceptible HHTg model of metabolic syndrome.


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

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