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| Status |
Public on Mar 05, 2019 |
| Title |
Liver X Receptor α Activation Enhances Cholesterol Secretion in Lactating Mammary Epithelium |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
We profiled differential gene expression in vivo between pregnant day 14 (secretory differentiation) and lactation day 4 (established secretory activation) using isolated mouse mammary epithelial cells depleted of the mammary adipocytes.
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 gland 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 are upregulated sharply at the onset of 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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| Overall design |
The isolated mammary epithelial cells from pregnant day 14 and lactation day 4 mice were investigated
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| Contributor(s) |
Grinman DY, Careaga VP, Wellberg EA, Dansey MV, Kordon EC, Anderson SM, Maier MS, Burton G, MacLean PS, Rudolph MC, Pecci A |
| Citation(s) |
30964702 |
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| Submission date |
Oct 25, 2018 |
| Last update date |
May 31, 2022 |
| Contact name |
Michael C. Rudolph |
| E-mail(s) |
Michael-rudolph@ouhsc.edu
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| Organization name |
OUHSC
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| Department |
Physiology
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| Lab |
Rudolph Lab
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| Street address |
975 NE 10th St. BRC North rm 364
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| City |
Oklahoma City |
| State/province |
OK |
| ZIP/Postal code |
73104 |
| Country |
USA |
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| Platforms (1) |
| GPL11533 |
[MoGene-1_1-st] Affymetrix Mouse Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA498520 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE121819_P14_vs_Lac4_MATRIX_FILE.xlsx |
4.3 Mb |
(ftp)(http) |
XLSX |
| GSE121819_RAW.tar |
34.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
| Processed data are available on Series record |
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