Effect of diet during pregnancy and lactation on the activity of HMG-CoA reductase in the developing rat

Wistar rats were fed a control diet or a diet containing either cholestyramine or high fat and cholesterol throughout gestation and the first 14 d of lactation. New-born litters were cross-fostered from rats fed the control diet to rats fed either cholestyramine or high fat and cholesterol, or from rats fed cholestyramine to rats fed the control diet. Hepatic hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase activity, plasma cholesterol and triglycerides were assayed on gestation d 20 and postnatal d 8, 14, 22 and 30. Cholestyramine had no effect on maternal or fetal plasma lipid levels but increased fetal hepatic HMG-CoA reductase activity by approximately 50%. The increased reductase activity persisted on postnatal d 8 and 14. Control pups suckled by dams fed cholestyramine also had significantly increased HMG-CoA reductase activities on postnatal d 8 and 14. The high fat and cholesterol diet significantly increased maternal plasma cholesterol but had no effect on HMG-CoA reductase activity in the fetus or suckling pups. Neither cholestyramine nor high fat and cholesterol altered the rat milk cholesterol levels. The studies demonstrate that HMG-CoA reductase activity in the developing rat can be altered by factors dependent on maternal diet. They do not support a hypothesis for regulation by maternal dietary or milk cholesterol supply.