Potential involvement of PPARs in the inhibition of mammary lipid synthesis during diet-induced milk fat depression

• Published in: Journal of dairy science 2024-11
• Main Authors: Haile, A., Oliveira, D.E., Boisclair, Y.R., Bauman, D.E., Harvatine, K.J.
• Format: Article
• Language: English
• Subjects: biohydrogenation; conjugated linoleic acid; PPAR-γ
• ISSN: 0022-0302; 1525-3198; 1525-3198
• DOI: 10.3168/jds.2024-25575

The objective of this study was to evaluate the possible role of the peroxisome proliferator-activated receptors (PPARs: PPAR-α, PPAR-β/δ, and PPAR-γ) in diet and conjugated linoleic acid (CLA)-induced milk fat depression (MFD) in dairy cows. We hypothesized that the expression of PPARs, which regulate lipid metabolism and bind to polyunsaturated fatty acids, could be modulated by biohydrogenation intermediates that induce MFD, thereby interfering with milk fat synthesis. First, tissue profiling revealed that PPAR-α and PPAR-β/δ had low expression in mammary tissue compared with the liver. A comparison of lactating and nonlactating tissue from the same cows showed that expression of the PPARs did increase during lactation. Mammary expression of the PPARs during MFD was then observed in 9 mid-lactation cows in a 3x3 Latin square design with MFD induced by a 3-d intravenous infusion of trans-10,cis-12 CLA or feeding a high-oil/low-forage diet. The expression of the PPARs remained largely unaltered during CLA and diet-induced MFD, except for an increase in PPAR-α target genes CPT1A and ACADVL that are involved in β-oxidation. The interaction of PPAR-γ chemical agonist Troglitazone and antagonist T0070907 and CLA was then investigated in bovine mammary epithelial cells (MAC-T). The activation and inhibition of PPAR-γ did not overcome trans-10,cis-12 CLA inhibition of lipogenesis despite the agonist stimulating PPAR-γ expression. Furthermore, PPAR-γ activation did not modify the expression of lipogenic genes. Overall, the results fail to support a functional role of the PPARs in the inhibition of lipogenesis during MFD in dairy cows.