Liver X Receptor alfa Activation Increases Cholesterol Abundance In Mouse Milk.

MACLEAN, PS; CAREAGA V.P; ADALI PECCI; MAIER M. S; GRINMAN DG; KORDON E; ; RUDOLPH, M

Conferencia; Gordon Research Conferences in Mammary Gland Biology; 2017

LXRs are transcription factors activated by cholesterol metabolites whose target genes participate in the de novo triglycerides synthesis and cholesterol transport in many tissues. By using different in vitro and in vivo murine models and a variety of experimental approaches, this work aims to elucidate the LXR contribution in mouse mammary lipid production. Here, we report that LXRs are expressed in a mouse mammary epithelial cell line, its mRNA abundance increases throughout differentiation and LXRα?s expression levels are higher than those of LXRβ. Upon pharmacological activation, LXRs upregulate the expression of several target genes involved in lipid synthesis and transport and also enhance citoplasmic lipid droplet accumulation. Correspondingly, we have found that LXRα protein levels increase through lactation compare to pregnancy in mouse mammary epithelial enriched fractions (MECs) and, when treated with a commercial LXR agonist, mice exhibited increased milk cholesterol percentage during lactation accompanied with an increase in mRNA levels of SREBP1c, another master regulator of lipid metabolism, in MECs. Overall, these results suggest that LXRα would be a relevant player in the mammary epithelium by regulating cholesterol transport into the milk