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The Liver X Receptor (LXR) is functionally active in the fetal mouse liver
Author(s) -
Plösch Torsten,
Straten Esther M.E.,
Huijkman Nicolette C.A.,
Baller Juul F.W.,
Kuipers Folkert
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a610-a
Subject(s) - liver x receptor , endocrinology , medicine , lipogenesis , fetus , agonist , triglyceride , biology , fatty liver , cholesterol , nuclear receptor , lipid metabolism , receptor , pregnancy , transcription factor , gene , biochemistry , genetics , disease
The Liver X Receptors LXRα/β are vitally important in regulating cholesterol and fatty acid metabolism in the adult. Aim of this study was to elucidate the role of LXR in the fetal mouse liver. Methods: Pregnant C57BL/6 mice were fed a diet containing the synthetic LXR agonist T0901317 from day 10.5 pc on. In fetuses and dams, gene expression and lipid levels were monitored. Results: In the mouse fetus, hepatic expression of LXR target genes (e.g., Srebp1c , Fas and Abcg5 ) is low during gestation and increases after birth. Lxra itself is expressed at ~40 % of adult levels, whereas the expression of Lxrb is 2.5–3 times higher than in adult control liver. Upon administration of T0901317, LXR target genes are activated in the fetal liver: expression of the cholesterol transporter Abcg5 is 45 times induced. Expression of Srebp1c and Fas is increased 2.0‐ to 5.3‐fold and 1.7‐ to 2.0‐fold, respectively. Consequently, triglyceride concentrations in fetal liver and plasma are raised up to 2.7‐ and 1.5‐fold. Cholesterol levels in plasma are doubled upon treatment, whereas hepatic cholesterol concentrations are unchanged. Conclusion: LXR is functionally active in fetal mouse liver when stimulated with the synthetic agonist T0901317. Similar to adult mice, cholesterol homeostasis and de novo lipogenesis can be influenced experimentally by administration of this agonist. Supported by the Dutch Heart Foundation (2004T048).