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1 Endocrinology & Metabolism, University of Southampton, Southampton, United Kingdom
2 Centre for Developmental Origins of Health and Disease, University of Southampton, Southampton, United Kingdom
3 Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom
* To whom correspondence should be addressed. E-mail: JZhang{at}soton.ac.uk.
Maternal dietary Fe restriction reduced fasting plasma cholesterol and triglyceride (TG) concentrations in the fetuses as well as decreased plasma TG levels in the adult offspring. To investigate how maternal Fe restriction was affecting fetal lipid metabolism, we investigated whether there were changes in liver lipid metabolism in the full-term fetuses. There was a ~27% (p < 0.05) increase in cholesterol but ~29% reduction (p = 0.01) in TG concentrations in the liver of the Fe restricted fetuses. Hepatic mRNA levels of cholesterol 7
hydroxylase (CYP7
), and liver X receptor-
(LXR
) were reduced by ~50% (p < 0.01) and ~34%
(p < 0.01) respectively. As LXR
regulates expression of sterol response element binding protein-1c expression (SREBP-1c), we measured SREBP-1c expression. There was a ~43% (p < 0.001) reduction in mRNA levels of SREBP-1c and its response genes including acetyl-CoA carboxylase by ~35% (p = 0.01), fatty acid synthase by ~18% (p = 0.05) and diacylglycerol acyltransferase by ~19% (p = 0.03). Furthermore, protein levels of CD36 were reduced by ~27% (p = 0.02) in Fe restricted fetuses. In conclusion, changes in liver cholesterol and TG concentrations in Fe restricted fetuses may be coordinated through reduced expression of heme-containing CYP7
and its regulator LXR
, mainly via down regulation of expression of genes in bile acid synthesis and fatty acid synthesis pathways.
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