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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 297/5/E1171    most recent 00021.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by van Straten, E. M. E. Articles by Plösch, T. PubMed PubMed Citation Articles by van Straten, E. M. E. Articles by Plösch, T.

Fetal liver X receptor activation acutely induces lipogenesis but does not affect plasma lipid response to a high-fat diet in adult mice

¹Departments of Pediatrics and ²Laboratory Medicine, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Submitted 9 January 2009 ; accepted in final form 26 August 2009

There is increasing evidence that the metabolic state of the mother during pregnancy affects long-term glucose and lipid metabolism of the offspring. The liver X receptors (LXR) and -β are key regulators of cholesterol, fatty acid, and glucose metabolism. LXRs are activated by oxysterols and expressed in fetal mouse liver from day 10 of gestation onward. In the present study, we aimed to elucidate whether in utero pharmacological activation of LXR would influence fetal fatty acid and glucose metabolism and whether this would affect lipid homeostasis at adult age. Exposure of pregnant mice to the synthetic LXR agonist T0901317 increased hepatic mRNA expression levels of Lxr target genes and hepatic and plasma triglyceride levels in fetuses and dams. T0901317 treatment increased absolute de novo synthesis and chain elongation of hepatic oleic acid in dams and fetuses. T0901317 exposure in utero influenced lipid metabolism in adulthood in a sex-specific manner; hepatic triglyceride content was increased (+45%) in male offspring and decreased in female offspring (–42%) when they were fed a regular chow diet compared with untreated sex controls. Plasma and hepatic lipid contents and hepatic gene expression patterns in adult male or female mice fed a high-fat diet were not affected by T0901317 pretreatment. We conclude that LXR treatment of pregnant mice induces immediate effects on lipid metabolism in dams and fetuses. Despite the profound changes during fetal life, long-term effects appeared to be rather mild and sex selective without modulating the lipid response to a high-fat diet.

fetus; lipid metabolism; gestation; long-term effects