Maternal dietary iron restriction modulates hepatic lipid metabolism in the fetuses

Abstract

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 7α hydroxylase and liver X receptor-α (LXRα) were reduced by ∼50% ( P < 0.01) and ∼34% ( P < 0.01), respectively. As LXRα regulates expression of sterol response element binding protein-1c (SREBP-1c) expression, we measured SREBP-1c expression. There was an ∼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 cholesterol 7α hydroxylase and its regulator LXRα, mainly via downregulation of expression of genes in bile acid synthesis and fatty acid synthesis pathways.