The Effects of Intra-Ductal Mammary Administration of Orexin-A Antagonist (SB-334867) on the PPARγ and SREBP1c Gene Expression and Serum Adiponectin Levels in Lactating Rats

Abstract

Introduction: Orexin A and adiponectin are involved in controlling metabolism and energy distribution in the body during lactation. Lactation is a process with high demand for lipid synthesis. Peroxisome proliferator-activated receptor gamma (PPARγ) and sterol regulatory element-binding protein 1 (SREBP1c) are two transcription factors that regulate milk lipid synthesis. The goal of this study was to assess the effects of mammary administration of the orexin A receptor antagonist on the expression of PPARγ and SREBP1c genes as well as serum adiponectin levels in the lactating rats. Methods: Orexin A receptor antagonist (SB-334867) was injected intraductal into the mammary glands of lactating female rats at three doses of 1, 2 and 4 μg/kg BW in a solvent volume of 50 μL. The gene expressions of PPARγ and SREBP1c were measured using real-time polymerase chain reaction (PCR), along with serum levels of adiponectin using ELISA. Results: The results of quantitative RT-PCR showed a significant decrease in the relative expression of PPARγ and SREBP1c genes compared to that of the control group. The rate of reduction at a dose of 4 µg/kg BW SB was greater than the doses of 1 and 2 µg/kg BW SB-334867. The serum levels of adiponectin significantly decreased in the 4 µg/kg BW SB group compared to that of the control group.Conclusion: These results indicated that intra-mammary administration of 4 µg/kg orexin-A antagonist in lactating rats decreased the gene expression of two transcription factors involved in milk fat synthesis, accompanying by a reduction in serum adiponectin level.