Effect of Dietary Cholesterol and Cholestyramine on Developmental Pattern of 3-Hydroxy-3-Methylglutaryl-CoA Reductase

Abstract

Supplementation of the diet with 2% cholesterol suppressed the increase observed in the hepatic and intestinal 3-hydroxy-3-methylglutaryl-CoA reductase activity from normally fed chicks during the first days after hatching. Cholestyramine feeding clearly increased both hepatic and intestinal reductase activities. In contrast, brain reductase did not show significant changes by cholesterol or choelstyramine feeding. Dietary cholesterol produced a clear increase in the cholesterol/lipidic phosphorus molar ratio of hepatic and intestinal microsomal membranes. However, this molar ratio did not change by cholestyramine feeding during postnatal development. Both dietary cholesterol and cholestyramine had practically no effect on the cholesterol/lipidic phosphorus molar ratio of brain microsomes. The relationship between the inhibition of reductase activity by dietary cholesterol and the increase of cholesterol/lipidic phosphorus molar ratio is in agreement with a mechanism of regulation of both hepatic and intestinal reductase by alterations of membrane fluidity, mechanism that would be already operative during the neonatal period.

Research Communications

“…29,38 This high level was also maintained during further development (21-28 days). 41 A similar inhibition of reductase activity by cholesterol feeding also was observed in chick intestine 40 and in isolated enterocytes from chick duodenum, jejunum, and ileum, 42 although in this tissue differences between peak and nadir values were always smaller than those observed in liver. 43 The hypercholesterolemic effect of cholesterol was generally accompanied by the accumulation of cholesterol in liver, thus interfering with the hepatic cholesterogenesis.…”

“…39 On the other hand, the clear inhibition of HMG-CoA reductase activity induced by coconut oil plus cholesterol feeding is in agreement with that previously observed in neonatal chicks that were fed a diet supplemented with 2% cholesterol during the 2 first weeks after hatching. 40 This inhibition was found when animals were euthanized approximately 12 hours after food deprivation, as in this work. Levels of HMG-CoA reductase activity in control chicks were practically similar to those observed in the present work.…”

“…In fact, dietary cholesterol supplementation to the newborn chick after 10 to 15 days produced a near 10-fold increase in the hepatic esterified cholesterol, whereas no significant variations were found in free cholesterol. The same dietary manipulation induced a significant inhibition not only of HMG-CoA reductase activity 40 but also of mevalonate incorporation into total nonsaponifiable lipids, 17,35 as well as in mevalonate 5-pyrophosphate decarboxylase activity. 44 A fraction of lanosterol derivatives and cholesterol precursors accumulated after cholesterol feeding may be responsible for the HMG-CoA reductase inhibition 45,46 as well as for the decrease of cholesterol synthesis from mevalonate.…”

Influence of Cholestyramine Feeding on Mevalonate-Activating Enzymes

“…Cholestyramine treatment results in hypocholesterolemia and in higher rates of cholesterol synthesis. Thus, in pre vious studies it has been demonstrated that both liver and intestinal HMG-CoA reduc tase of chicks fed 3% cholestyramine from hatching were increased with respect to con trols after 7 days of treatment [1]. The present results obtained in intestine consti tute, to our knowledge, the first report on the effect of cholestyramine on phosphorylation and decarboxylation of MVA in this organ.…”

Changes in cultured arterial smooth muscle cells isolated from chicks upon cholesterol feeding

“…We have also used chicks previously to study lipid metabolism after cholesterol administration (30)(31)(32)(33). The aim of this study was to develop a cell-culture avian model to look into the effect of a cholesterol diet on the transformation of SMC in vivo.…”