CONICET | Buscador de Institutos y Recursos Humanos

Liver x receptors L:4s a/b are transcription factors that actas cholesterol sensors. When upregulated, intracellular cholesterolis metabolized to oxysterols, the natural ligands of the L:4s.Activated L:4s enhance the expression of enzymes that controllipid synthesis and transport and even modulate the inflammatoryresponse. )ene expression studies revealed that activation of fattyacid synthesis in the mammary epithelium occurs in responseto parturition and the onset of lactation. This increased expressionof lipogenic genes is significantly larger than their relativeexpression in the liver, supporting the hypothesis that the mammarygland is undergoing changes to fulfill milM lipid levels. 1uraim Yas to identify Yhether the L:4s regulate the expression oflipogenic genes in epithelial mammary cells and thus to study itsparticipation in milk lipid production and transport during lactation.9eyve found that in the normal mouse mammary epithelial cellline HC L:4s activation induces Fatty Acid Synthase FASand A$CA, an AT2dependent cholesterol transporter expression.9e also identified that, in purified mouse mammary glandepithelial cells /ECs, L:4aŏs protein levels increase along Yithlactation progress. /oreover, incubation of /ECs from lactatingday mammary glands Yith the L:4 synthetic agonist )9)9 induced FAS expression .v. fold vs. non treatedcells. Finally, Ye performed FA/E analysis on milM collected fromlactating mothers treated for h Yith )9 or vehicle to quantifythe milM lipid profile. +n concordance Yith FAS induction, Ye foundthat the amount of C palmitic acid, the main product of FASactivity, increased in )9 treated mice suggesting that L:4a mayregulate the de novo lipogenesis in the mammary epithelium. Thebetter characterization of L:4ŏs effects Yill provide relevant dataon milM fat production mechanism that Yould gain interest in dairyindustry due to their putative capacity to modify lipid composition