Liver X Receptor α Activation Enhances Cholesterol Secretion in Lactating Mammary Epithelium.
Liver X Receptor α Activation Enhances Cholesterol Secretion in Lactating Mammary Epithelium.
Am J Physiol Endocrinol Metab. 2019 Apr 09;:
Authors: Grinman DY, Careaga VP, Wellberg EA, Dansey MV, Kordon EC, Anderson SM, Maier MS, Burton G, MacLean PS, Rudolph MC, Pecci A
Abstract
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. Cumula...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Grinman DY, Careaga VP, Wellberg EA, Dansey MV, Kordon EC, Anderson SM, Maier MS, Burton G, MacLean PS, Rudolph MC, Pecci A Tags: Am J Physiol Endocrinol Metab Source Type: research
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