Effect of premature weaning on the regulation of cholesterol and lipoprotein metabolism in adult guinea pigs.

Abstract

The effects of premature weaning at two days of age on cholesterol and lipoprotein metabolism were studied in adult guinea pigs. Both normally (control) and prematurely weaned guinea pigs were fed a non-purified diet (basal diet). At 8 weeks of age control and prematurely weaned animals were divided into three groups, and were fed either the basal diet, or basal diet containing either 0.25% cholesterol or 1.1% cholestyramine for 4 weeks. Prematurely weaned guinea pigs fed the basal diet as adults exhibited a significant increase of 1.7-fold in hepatic 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity and a 1.4-fold increase in plasma cholesterol levels, mainly in the low-density lipoprotein (LDL) fraction (P < 0.05). In addition, the number of LDL receptors of hepatic membranes was significantly reduced by 56% in prematurely weaned guinea pigs compared to controls. Mass ratios of core (triglyceride and cholesteryl ester) to surface (free cholesterol, protein, and phospholipid) components of LDL were significantly higher in the prematurely weaned animals relative to normally weaned animals (P < 0.05). However, there was no change in particle size with variation in treatment. In vitro incubation of LDL with high density lipoprotein and cholesterol ester transfer protein demonstrated a 2-fold increase in cholesteryl esters transferred to LDL in the prematurely weaned animals compared to controls. Addition of dietary cholesterol increased plasma and hepatic cholesterol levels, and decreased hepatic HMG-CoA reductase activity and receptor-mediated LDL binding in the control animals. In contrast, prematurely weaned animals did not show a significant increase in plasma cholesterol levels. Cholestyramine intake decreased plasma cholesterol in the normally weaned but not in prematurely weaned guinea pigs. Premature weaning resulted in a significant reduction in hepatic cholesterol levels in animals fed cholestyramine. Receptor-mediated LDL binding increased in animals fed cholestyramine compared to animals fed the basal diet and premature weaning did not alter this response. These data indicate that premature weaning alters in vivo cholesterol metabolism of adult guinea pigs resulting in increased plasma cholesterol levels, hepatic HMG-CoA reductase activity and CETP activity, and decreased levels of hepatic LDL receptors. Premature weaning also alters the regulatory responses to feedback suppression and metabolic induction of plasma lipoprotein cholesterol metabolism.