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The Journal of Lipid Research, Vol. 39, 2237-2249, November 1998
Copyright © 1998 by Lipid Research, Inc.
Effect of pregnancy and lactation on lipoprotein and cholesterol metabolism in the rat
Jeffery L. Smitha,
Steven R. Leara,
Trudy M. Forteb,
William Koa,
Mara Massimia, and
Sandra K. Ericksona
a Department of Medicine, University of California, San Francisco, and Department of Veterans Affairs Medical Center, San Francisco, CA 94121
b Life Sciences Division, Lawrence Berkeley Laboratory, University of California, Berkeley, CA 94720
Correspondence to:
Sandra K. Erickson.
Origins of hyperlipidemia and cholestasis that occur during pregnancy were investigated by examining expression of key elements related to plasma and hepatic cholesterol metabolism during pregnancy, lactation, and post-lactation in the rat model. Among major findings were: during pregnancy, the activities of hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase, acyl coenzyme A:cholesterol acyltransferase, acyl coenzyme A:diacylglycerol acyltransferase, cholesterol 7 -hydroxylase, cholesterol ester hydrolases, low density lipoprotein receptors, LRP, and mdr2 were significantly lower or similar to non-pregnant controls while SR-B1 was elevated. Once lactation began, reductase, cholesterol acyltransferase, 7 -hydroxylase activities, low density lipoprotein receptors, and mdr2 increased while SR-B1 decreased. In later stages of lactation most hepatic elements returned to near control levels. Plasma cholesterol levels were higher than control at birth and during lactation with increase in LDL-size particles. By 24 h post-lactation, plasma triglycerides were 3.7-fold higher while cholesterol remained unchanged. Very large lipoproteins were present while LDL-size particles were now absent. Hepatic cholesterol acyltransferase had decreased to 27% of control while diacylglycerol acyltransferase increased 3-fold and low density lipoprotein receptors doubled. Most elements were normalized 3 weeks after weaning except for LRP and low density lipoprotein receptors which were elevated.
These studies provide an integrated picture of expression of key elements of hepatic and plasma cholesterol metabolism during pregnancy and lactation and advance understanding of hyperlipidemia and cholestasis during these states.Smith, J. L., S. R. Lear, T. M. Forte, W. Ko, M. Massimi, and S. K. Erickson. Effect of pregnancy and lactation on lipoprotein and cholesterol metabolism in the rat. J. Lipid Res. 1998. 39: 22372249.
Supplementary key words:
liver, ACAT, cholesterol 7 -hydroxylase, SR-B1, mdr2, LDL receptor, LRP, apolipoproteins, DGAT, cholesterol ester hydrolases

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Copyright © 1998 by the American Society for Biochemistry and Molecular Biology.
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