Effect of intraductal drug delivery of orexin receptor antagonists into lactating rat mammary gland on milk cholesterol metabolism by regulating Fas and Hmgcr genes

In recent years, many studies have demonstrated that the system of orexin plays a pivotal role in regulating lipogenesis enzymes. However, its effect on the mammary glands is not entirely known. This study answers the question of whether intra-ductal injection of orexin antagonists (OX1RA and OX2RA) into the mammary glands can result in the expression of fatty acid synthase (Fas) and HMG-CoA reductase (Hmgcr) genes and the secretion of cholesterol in lactating female rats or not. To this end, 42 Lactating rats were randomly divided into experimental groups including a control group and groups receiving OX1RA and OX2RA intraductal (with doses of 5, 10, and 20 µg/kg, i.duc). Milk samples were collected for cholesterol testing. Using specific primers for each gene, the target genes were measured via real-time PCR. Data differences were considered significant with P <0.05. PCR exhibited that the injection of orexin antagonists significantly reduced Fas and Hmgcr gene expression. Moreover, the injection of antagonists significantly reduced milk cholesterol. Intra-mammary injection of orexin antagonists reduces milk cholesterol levels by affecting the expression of Fas and Hmgcr genes.