Effect of pregnancy and lactation on lipoprotein and cholesterol metabolism in the rat

Abstract

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-3methylglutaryl 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 postlactation, 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.-

Breastfeeding duration and subsequent risk of mortality among US women: A prospective cohort study

“…Animal studies have demonstrated that breastfeeding plays an important role in mobilizing stored fat, 24 reestablishing glucose homeostasis, 24 , 25 regulating insulin secretion, 26 and promoting lipid metabolism after delivery. 27 Population evidence from observational studies also suggests that breastfeeding is associated with improved glucose metabolism and pancreatic beta-cell function, 28 more favourable lipid profiles, 29 and reduced weight loss and risk of metabolic diseases. 30 Meanwhile, several randomised controlled trials have demonstrated that greater intensity of lactation is associated with greater postpartum weight loss.…”

A lipoprotein-containing particle is transferred from the serum across the mammary epithelium into the milk of lactating mice

“…Over the course of a 21-day lactation, a female mouse nursing a large litter will produce about 20 g of milk fat, containing about 100 mg of cholesterol. Smith et al (29) studied the effect of lactation on plasma lipoproteins in rats. Whereas the LDL content of plasma was increased in lactation, very low density lipoprotein (VLDL)-sized particles were not apparent.…”

A rapid calcium precipitation method of recovering large amounts of highly pure hepatocyte rough endoplasmic reticulum

“…Acyl coenzyme A:cholesterol acyltransferase (ACAT ) localized largely in the RER (35,36) and acyl coenzyme A:diacylglycerol acyltransferase (DGAT ) localized in both RER and smooth ER (37,38) were measured by enzyme activity as described previously (39). Albumin, and apolipoproteins A-I, E, A-IV, and C were estimated in aliquots of whole liver homogenate and intact RER by SDS gel electrophoresis and Western blotting using specific antisera provided by Dr. Karl Weisgraber as described previously (28).…”

“…Albumin, and apolipoproteins A-I, E, A-IV, and C were estimated in aliquots of whole liver homogenate and intact RER by SDS gel electrophoresis and Western blotting using specific antisera provided by Dr. Karl Weisgraber as described previously (28). ApoB was estimated by SDS gel electrophoresis and Western blot as described previously (39). Microsomal triglyceride transfer protein (MTP) was estimated by SDS gel electrophoresis and Western blot using specific antisera for MTP pro-vided by Dr. David Gordon.…”