HMGR overexpression and interference affect the expression of steroidogenic genes and cholesterol content in bovine intramuscular adipocytes

Abstract

Previously, we found that mevalonic acid stimulates 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) expression in bovine intramuscular adipocytes to influence adipocyte differentiation. However, any direct links among HMGR, steroidogenic genes, and cholesterol content remain unclear. RNA-Seq was conducted to determine the differences between the gene expression profiles of bovine adipocytes containing different HMGR expression constructs. In total, 10,234 differentially expressed genes (DEGs) were found. Of these, 35 and 6 DEGs between the control and the overexpression groups were functionally related to lipid and energy metabolism, respectively. In addition, 43 and 8 DEGs between the control and the HMGR inhibition groups were related to lipid and energy metabolism, respectively. Several DEGs related to lipid and energy metabolism were also identified between the HMGR overexpression group and the HMGR interference group, and many DEGs were correlated positively or negatively with the overexpression or inhibition of HMGR. We also found that, following the activation or inhibition of the HMGR gene, AMP-activated protein kinase (AMPK) and sirtuin type 1 (SIRT1) had opposite expression patterns in bovine intramuscular adipocytes. Interestingly, the HMGR gene was downregulated when HMGR was overexpressed, and upregulated when HMGR was inhibited. Our findings establish a theoretical understanding of signaling pathways involved in cholesterol synthesis by elucidating the relationships between key genes.