Nutrigenomic Effect of Saturated and Unsaturated Long Chain Fatty Acids on Lipid-Related Genes in Goat Mammary Epithelial Cells: What Is the Role of PPARγ?

A prior study in bovine mammary (MACT) cells indicated that long-chain fatty acids (LCFA) C16:0 and C18:0, but not unsaturated LCFA, control transcription of milk fat-related genes partly via the activation of peroxisome proliferator-activated receptor gamma (PPAR gamma). However, in that study, the activation of PPAR gamma by LCFA was not demonstrated but only inferred. Prior data support a lower response of PPAR gamma to agonists in goat mammary cells compared to bovine mammary cells. The present study aimed to examine the hypothesis that LCFA alter the mRNA abundance of lipogenic genes in goat mammary epithelial cells (GMEC) at least in part via PPAR gamma. Triplicate cultures of GMEC were treated with a PPAR gamma agonist (rosiglitazone), a PPAR gamma inhibitor (GW9662), several LCFA (C16:0, C18:0, t10,c12-CLA, DHA, and EPA), or a combination of GW9662 with each LCFA. Transcription of 28 genes involved in milk fat synthesis was measured using RT-qPCR. The data indicated that a few measured genes were targets of PPAR gamma in GMEC (SCD1, FASN, and NR1H3) while more genes required a basal activation of PPAR gamma to be transcribed (e.g., LPIN1, FABP3, LPL, and PPARG). Among the tested LCFA, C16:0 had the strongest effect on upregulating transcription of measured genes followed by C18:0; however, for the latter most of the effect was via the activation of PPAR gamma. Unsaturated LCFA downregulated transcription of measured genes, with a lesser effect by t10,c12-CLA and a stronger effect by DHA and EPA; however, a basal activation of PPAR gamma was essential for the effect of t10,c12-CLA while the activation of PPAR gamma blocked the effect of DHA. The transcriptomic effect of EPA was independent from the activation of PPAR gamma. Data from the present study suggest that saturated LCFA, especially C18:0, can modulate milk fat synthesis partly via PPAR gamma in goats. The nutrigenomic effect of C16:0 is not via PPAR gamma but likely via unknown transcription factor(s) while PPAR gamma plays an indirect role on the nutrigenomic effect of polyunsaturated LCFA (PUFA) on milk fat related genes, particularly for CLA (permitting effect) and DHA (blocking effect).