Novel carboxamide derivatives increase lipoprotein lipase gene expression in endothelial and adipose tissues of triton WR- 1339 induced hyperlipidemic rats.

Hyperlipidemia is a heterogeneous disorder that refers to increased lipid levels in the blood. The purpose of this study was to investigate the molecular effects of novel carboxamide derivatives on a hyperlipidemic male rat model induced by Triton WR-1339 in comparison to fenofibrate using liver, endothelial, and adipose tissue samples. Nitrofuran-2-carboxamide derivatives were compared to fenofibrate to evaluate their molecular hypolipidemic actions. The gene expression profiles of pathways related to triglycerides including PPAR-alpha and beta-oxidation pathways were evaluated in an acute hyperlipidemia rat model using RT-PCR followed by protein-protein interaction networks that were produced using the STRING database. The three novel compounds showed a significant effect on the lipid profile. Several genes were reported to be overexpressed by Triton WR-1339, including CPT1 A in liver tissue and APOE in adipose tissue. Most of the overexpressed genes were downregulated by carboxamide derivatives, with significant decreases in CPT1 A and APOE gene expression levels. On the other hand, several genes were reported to be downregulated by Triton WR-1339, including ACOX1 in liver tissue, LPL, ACADM and ACAA2 in endothelial tissue, and LPL and ACADM in adipose tissue. Most of the downregulated genes were significantly upregulated by carboxamide derivatives. In summary, the three novel compounds were found to improve hypertriglyceridemia with significant changes in gene expression of key enzymes in lipids metabolism, mainly LPL.