Peroxisome proliferator-activated receptor delta facilitates lipid secretion and catabolism of fatty acids in dairy goat mammary epithelial cells

In rodents, peroxisome proliferator-activated receptor delta (PPARD) is associated primarily with catabolism of fatty acids. However, the role of PPARD in regulating lipid metabolism in ruminant mammary gland remains unknown. In the present study, we assessed the mRNA abundance of PPARD at 3 stages of lactation in goat mammary tissue. Results revealed that PPARD had lower expression at peak lactation than in the nonlactating period. Luciferase assays revealed that GW0742 (GW), a specific PPARD ligand, enhanced the activity of the PPARD response element in goat mammary epithelial cells. Activation of PPARD by GW selectively upregulated the expression of genes related to fatty acid activation (ACSL1), lipid droplet formation (PLIN2), and transport (FABP4), and had no effect on genes involved in de novo fatty acid synthesis (ACACA and FASN), desaturation (SCD), hydrolysis and oxidation (PNPLA2 and CPT1A), transport and uptake (FABP3 and CD36), or triacylglycerol synthesis (DGAT1 and AGPAT6) in goat mammary epithelial cells. In contrast, knockdown of PPARD using small interfering RNA dramatically decreased the expression of genes related to fatty acid activation (ACSL1) and lipid formation (PLIN2) and increased the expression of genes related to fatty acid transport (FABP3) and triacylglycerol synthesis (AGPAT6 and DGAT1). The expression of genes related to fatty acid synthesis (FASN), hydrolysis (PNPLA2), and fatty acid oxidation (CPT1A) was downregulated significantly only after knockdown of PPARD in cells incubated with GW. We observed no significant change in fatty acid profiles. However, the total cellular triacylglycerol increased after knockdown of PPARD in goat mammary epithelial cells plus GW. Collectively, these results highlight an important role for PPARD in the homeostasis of ruminant mammary cells by facilitating fatty acid activation and lipid droplet formation and secretion.