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Liver X Receptor α Activation Enhances Cholesterol Secretion in Lactating Mammary Epithelium.

08:00 EDT 9th April 2019 | BioPortfolio

Summary of "Liver X Receptor α Activation Enhances Cholesterol Secretion in Lactating Mammary Epithelium."

Liver-X-Receptors are ligand-dependent transcription factors activated by cholesterol metabolites. These receptors induce a suite of target genes required for de novo synthesis of triglycerides and cholesterol transport in many tissues. Two different isoforms -LXRα and LXRβ- have been well characterized in liver, adipocytes, macrophages and intestinal epithelium among others, but their contribution to cholesterol and fatty acid efflux in the lactating mammary epithelium is poorly understood. We hypothesize that LXR regulates lipogenesis during milk fat production in lactation. Global mRNA analysis of mouse mammary epithelial cells (MECs) revealed multiple LXR/RXR targets upregulated sharply early in lactation compared to mid-pregnancy. LXRα is the primary isoform and its protein levels increase throughout lactation in MECs. The LXR agonist GW3965 markedly induced several genes involved in cholesterol transport and lipogenesis and enhanced cytoplasmic lipid droplet accumulation in the HC11 MEC cell line. Importantly, in vivo pharmacological activation of LXR increased the milk cholesterol percentage and induced Srebp1c and Abca7 expression in MECs. Cumulatively, our findings identify LXRα as an important regulator of cholesterol incorporation into the milk through key nodes of de novo lipogenesis, suggesting a potential therapeutic target in women with difficulty initiating lactation.

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Name: American journal of physiology. Endocrinology and metabolism
ISSN: 1522-1555
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Medical and Biotech [MESH] Definitions

An eph family receptor found in a variety of adult and embryonic tissues. Unlike the majority of proteins in this class there is little or no expression of EphB4 receptor in the BRAIN. It has been found at high levels in developing mammary glands and in invasive mammary tumors.

The most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. This protein serves as an acceptor for CHOLESTEROL released from cells thus promoting efflux of cholesterol to HDL then to the LIVER for excretion from the body (reverse cholesterol transport). It also acts as a cofactor for LECITHIN CHOLESTEROL ACYLTRANSFERASE that forms CHOLESTEROL ESTERS on the HDL particles. Mutations of this gene APOA1 cause HDL deficiency, such as in FAMILIAL ALPHA LIPOPROTEIN DEFICIENCY DISEASE and in some patients with TANGIER DISEASE.

A first generation selective estrogen receptor modulator (SERM). Like TAMOXIFEN, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue.

The processes of milk secretion by the maternal MAMMARY GLANDS after PARTURITION. The proliferation of the mammary glandular tissue, milk synthesis, and milk expulsion or let down are regulated by the interactions of several hormones including ESTRADIOL; PROGESTERONE; PROLACTIN; and OXYTOCIN.

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