Maternal dietary iron restriction modulates hepatic lipid metabolism in the fetuses.
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 approximately 27% (P < 0.05) increase in cholesterol but approximately 29% reduction (P = 0.01) in TG concentrations in the liver of the Fe-restricted fetuses. Hepatic mRNA levels of cholesterol 7alpha hydroxylase and liver X receptor-alpha (LXRalpha) were reduced by approximately 50% (P < 0.01) and approximately 34% (P < 0.01), respectively. As LXRalpha regulates expression of sterol response element binding protein-1c (SREBP-1c) expression, we measured SREBP-1c expression. There was an approximately 43% (P < 0.001) reduction in mRNA levels of SREBP-1c and its response genes, including acetyl-CoA carboxylase by approximately 35% (P = 0.01), fatty acid synthase by approximately 18% (P = 0.05), and diacylglycerol acyltransferase by approximately 19% (P = 0.03). Furthermore, protein levels of CD36 were reduced by approximately 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 7alpha hydroxylase and its regulator LXRalpha, mainly via downregulation of expression of genes in bile acid synthesis and fatty acid synthesis pathways.
Zhang
Junlong
J
Endocrinology and Metabolism Unit, Developmental Origins of Health and Disease Division, School of Medicine, University of Southampton, Southampton General Hospital, Southampton SO16 6YD, UK. JZhang@soton.ac.uk
Lewis
Rohan M
RM
Wang
Chunli
C
Hales
Nicholas
N
Byrne
Christopher D
CD
D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005333:Fetus / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D000090463:Iron Deficiencies; D050356:Lipid Metabolism; D008099:Liver / Q000196:embryology* / Q000378:metabolism; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011247:Pregnancy; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D000071518:Liver X Receptors; C000605215:Nr1h3 protein, rat; D057093:Orphan Nuclear Receptors; D018160:Receptors, Cytoplasmic and Nuclear; C497389:Srebf1 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014157:Transcription Factors; D014280:Triglycerides; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase