Influence of maternal cholestyramine treatment on cholesterol and bile acid metabolism in adult offspring.
To reduce ileal reabsorption of bile acids and to deplete hepatic cholesterol pools, female rats were fed a diet containing 5% (wt/wt) cholestyramine from 4 days prior to mating. Control rats were fed the same diet without cholestyramine. In one group on day 20 of gestation diet-fed dams and their fetuses were investigated. Additional pups were raised in litters of eight and nursed by their mothers for 30 days at which time they were weaned to the control diet. All dams were given the control diet from day 14 of lactation; at no time did neonates have access to cholestyramine. Offspring were raised until 3 months of age then fed the control, cholestyramine or a high fat, high cholesterol diet for 5 days. Maternal cholestyramine produced significant elevation of fetal hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase; fetal 7 alpha-hydroxylase (7 alpha-OH) activity, plasma cholesterol and triglyceride levels, however, were not significantly altered. The elevated HMG-CoA reductase activity persisted in liver and in addition was present in jejunum of 3-month-old male offspring challenged with the control or cholestyramine diet for 5 days. When challenged with the high fat, high cholesterol diet, male offspring from cholestyramine-treated dams had significantly higher plasma cholesterol levels but HMG-CoA reductase and 7 alpha-OH activity similar to controls. Maternal treatment had no apparent effect on plasma triglyceride or hepatic 7 alpha-OH in 3-month-old male offspring.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D002792:Cholestyramine Resin / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage; D005260:Female; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D007082:Ileum / Q000378:metabolism; D007583:Jejunum / Q000378:metabolism; D007774:Lactation / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008297:Male; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D002792:Cholestyramine Resin; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases