Identification of Central Genes and Regulatory Pathways Associated with Hyperlipidemia in Rats.

ABSTRACT

Hyperlipidemia is an independent risk factor for cardiovascular and cerebrovascular diseases. The transcriptomic data and the gene regulatory networks of hyperlipidemia are largely unclear. We analyzed the changes in liver gene expression and the serum levels of biochemical indicators in rats with hyperlipidemia induced by high-fat diet (HFD). The body weight, liver weight, and the serum levels of TG, TC, HDL-C, LDL-C, ALT, and AST were significantly higher in the hyperlipidemic rats compared to the healthy controls (P < 0.05). In addition, HFD feeding decreased the antioxidant capacity of the liver tissues and significantly increased the arteriosclerosis index (AI) (P < 0.05). There were 584 differentially expressed genes (DEGs) in the hyperlipidemia model compared to the control, with |log2FC|≥ 1 and P-adjust ≤ 0.05 as the thresholds. GO analysis of the DEGs revealed significant enrichment of 382 biological processes (BP), 18 cellular components (CC), and 40 molecular functions (MF). In addition, pathways related to bile secretion, cholesterol metabolism, and steroid hormone biosynthesis were significantly associated with hyperlipidemia. The key genes potentially involved in the blood lipid changes were Agt, Src, Gnai3, Cyp2c7, Cyp2c11, Cyp2c22, Apoa1, Apoe, and Srebf1. The genes and pathways identified in this study are potential intervention targets for hyperlipidemia and warrant further investigation.