Pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism

E. M. E. van Straten, N. C. A. Huijkman, J. F. W. Baller, F. Kuipers, T. Plosch*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

13 Citaten (Scopus)

Samenvatting

van Straten EM, Huijkman NC, Baller JF, Kuipers F, Plosch T. Pharmacological activation of LXR in utero directly influences ABC transporter expression and function in mice but does not affect adult cholesterol metabolism. Am J Physiol Endocrinol Metab 295: E1341-E1348, 2008. First published October 7, 2008; doi: 10.1152/ajpendo.90597.2008. Cholesterol is critical for several cellular functions and essential for normal fetal development. Therefore, its metabolism is tightly controlled during all life stages. The liver X receptors-alpha (LXR alpha; NR1H3) and -beta (LXR beta; NR1H2) are nuclear receptors that are of key relevance in coordinating cholesterol and fatty acid metabolism. The aim of this study was to elucidate whether fetal cholesterol metabolism can be influenced in utero via pharmacological activation of LXR and whether this would have long-term effects on cholesterol homeostasis. Administration of the LXR agonist T0901317 to pregnant mice via their diet (0.015% wt/wt) led to induced fetal hepatic expression levels of the cholesterol transporter genes Abcg5/g8 and Abca1, higher plasma cholesterol levels, and lower hepatic cholesterol levels compared with controls. These profound changes during fetal development did not affect cholesterol metabolism in adulthood nor did they influence coping with a high-fat/high-cholesterol diet. This study shows that the LXR system is functional in fetal mice and susceptible to pharmacological activation. Despite massive changes in fetal cholesterol metabolism, regulatory mechanisms involved in cholesterol metabolism return to a "normal" state in offspring and allow coping with a high-fat/high-cholesterol diet.

Originele taal-2English
Pagina's (van-tot)E1341-E1348
Aantal pagina's8
TijdschriftAmerican Journal of Physiology - Endocrinology and Metabolism
Volume295
Nummer van het tijdschrift6
DOI's
StatusPublished - dec-2008

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