Maternal dietary iron restriction modulates hepatic lipid metabolism in the fetuses
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 ~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 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 (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 7 hydroxylase and its regulator LXR?, mainly via downregulation of expression of genes in bile acid synthesis and fatty acid synthesis pathways.
cholesterol, cholesterol 7 alpha hydroxylase, liver x receptor-alpha, fetus
R104-R111
Zhang, Junlong
68a8fa77-c5db-4b34-aa9a-fbad6860155f
Lewis, Rohan M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Wang, Chunli
d9ec88ea-e4c5-41de-9ffc-4059aac94098
Hales, Nicholas
a2ed2f1f-d069-4a9a-9ec1-c117cca796b0
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
2005
Zhang, Junlong
68a8fa77-c5db-4b34-aa9a-fbad6860155f
Lewis, Rohan M.
caaeb97d-ea69-4f7b-8adb-5fa25e2d3502
Wang, Chunli
d9ec88ea-e4c5-41de-9ffc-4059aac94098
Hales, Nicholas
a2ed2f1f-d069-4a9a-9ec1-c117cca796b0
Byrne, Christopher D.
1370b997-cead-4229-83a7-53301ed2a43c
Zhang, Junlong, Lewis, Rohan M., Wang, Chunli, Hales, Nicholas and Byrne, Christopher D.
(2005)
Maternal dietary iron restriction modulates hepatic lipid metabolism in the fetuses.
American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 288 (1), .
(doi:10.1152/ajpregu.00343.2004).
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 7 hydroxylase 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 (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 7 hydroxylase and its regulator LXR?, mainly via downregulation of expression of genes in bile acid synthesis and fatty acid synthesis pathways.
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Published date: 2005
Keywords:
cholesterol, cholesterol 7 alpha hydroxylase, liver x receptor-alpha, fetus
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Local EPrints ID: 26158
URI: http://eprints.soton.ac.uk/id/eprint/26158
ISSN: 0363-6119
PURE UUID: 8fa8ac59-fce6-4789-9a2d-5fda58bd9ea7
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Date deposited: 19 Apr 2006
Last modified: 16 Mar 2024 03:21
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Author:
Junlong Zhang
Author:
Chunli Wang
Author:
Nicholas Hales
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