LIVER X RECEPTOR α MAY REGULATE FATTY ACID SYNTHASE IN MAMMARY EPITHELIAL CELLS DURING LACTATION

GRINMAN DIEGO; CAREAGA V; RUDOLPH M; MACLEAN P; MAIER MARTA; PECCI A

Mar del Plata

Congreso; LXI Reunion Anual de SAIC; 2016

SAIC

Liver x receptors (LXRs) α/β are transcription factors that act as cholesterol sensors. When upregulated, intracellular cholesterol is metabolized to oxysterols, the natural ligands of the LXRs. Activated LXRs enhance the expression of enzymes that control lipid synthesis and transport and even modulate the inflammatory response. Gene expression studies revealed that activation of fatty acid synthesis in the mammary epithelium occurs in response to parturition and the onset of lactation. This increased expression of lipogenic genes is significantly larger than their relative expression in the liver, supporting the hypothesis that the mammary gland is undergoing changes to fulfill milk lipid levels. Our aim was to identify whether the LXRs regulate the expression of lipogenic genes in epithelial mammary cells and thus to study its participation in milk lipid production and transport during lactation. We´ve found that in the normal mouse mammary epithelial cell line (HC11) LXRs activation induces Fatty Acid Synthase (FAS) and ABCA1, an ATP-dependent cholesterol transporter expression. We also identified that, in purified mouse mammary gland epithelial cells (MECs), LXRα?s protein levels increase along with lactation progress. Moreover, incubation of MECs from lactating day 5 mammary glands with the LXR synthetic agonist GW3965 (GW) induced FAS expression 2.96±0.21 fold vs. non treated cells. Finally, we performed FAME analysis on milk collected from lactating mothers treated for 24h with GW or vehicle to quantify the milk lipid profile. In concordance with FAS induction, we found that the amount of C16:0 (palmitic acid), the main product of FAS activity, increased in GW treated mice suggesting that LXRα may regulate the de novo lipogenesis in the mammary epithelium. The better characterization of LXR?s effects will provide relevant data on milk fat production mechanism that would gain interest in dairy industry due to their putative capacity to modify lipid composition.