Liver X Receptor alpha; Activation Increases Cholesterol Abundance In Mouse Milk

GRINMAN D.; RUDOLPH M; CAREAGA V.; KORDON E.; MAIER M.; MACLEAN, P.; PECCI A.

Congreso; Gordon Research Conference on Mammary Gland Biology; 2017

Liver X Receptor α Activation Increases Cholesterol Abundance In Mouse MilkLXRs are transcription factors activated by cholesterol metabolites whose target genes participate in the de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different LXR isoforms has been described: LXRα and LXRβ and their roles were characterized in liver, adipocytes, macrophages and intestinal epithelium among others. By using different in vitro and in vivo murine models and a variety of experimental approaches, this work aimed to elucidate the LXR contribution in mouse mammary lipid production during lactation. Here, we report that both LXRs isoforms are expressed in a mouse mammary epithelial cell line (HC11), being LXRα?s expression levels higher than LXRβ´s ones. Additionally, LXRs mRNA abundance increase throughout differentiation. Upon pharmacological activation, LXRs upregulate the expression of several target genes involved in lipid synthesis and cholesterol transport and also enhance citoplasmic lipid droplets accumulation. Correspondingly, we have found that LXRα protein levels increase through lactation compare to pregnancy in mouse mammary epithelial enriched fractions (MECs). Moreover, when i.p injected with a commercial LXR agonist, mice exhibited increased milk cholesterol percentage during lactation accompanied with an increase in mRNA SREBP1c levels in MECs. Overall, these results suggest that LXRα would be a relevant player in the mammary epithelium by regulating cholesterol transport into the milk.