Effect of cholesterol and cholestyramine feeding and of fasting on sterol synthesis in the liver, lleum, and lung of the guinea pig.
The effects of feeding diest containing either cholesterol (0.24% w/w) or cholestyramine (2.5% w/w) and of fasting on sterol synthesis in the liver, ileum, and lung of both male and female guinea pigs have been studied by measuring the incorporation by tissue slices of 14C-labeled acetate into total digitoninpredipitable sterols. Cholesterol feeding significantly decreased (P less than 0.05) sterol synthesis in the liver, ileum, and lung of the males and in the ileum of females. Cholestyramine feeding stimulated the rate of hepatic sterol synthesis 13-fold but did not significantly affect sterologenesis in the ileum. Sterol synthesis in the lung was significantly increased (P less than 0.05) but to a much lesser extent than in the liver. Fatty acid synthesis in the liver, ileum, and lung was not significantly affected by either cholesterol or cholestyramine feeding. In guinea pigs fasted for 24 hr, sterol synthesis was inhibited in all three tissues, the most pronounced effect occurring in the liver. Only in the lung was fatty acid synthesis significantly decreased (P less than 0.001) by  fasting. Cholesterol feeding resulted in increased concentrations of cholesterol in the plasma and liver. Cholestyramine feeding reduced plasma cholesterol concentration by 81% in females and by 64% in males. However, it did not significantly change the tissue cholesterol concentrations. Fasting resulted in a significant increase (P less than 0.05) in plasma cholesterol concentration but did not effect the concentration of cholesterol in the tissues. It was concluded that in the normal guinea pig, the feedback inhibition produced by both cholesterol and also possibly by bile acids suppresses sterol synthesis in the liver to very low rates compared to those in the small intestine, where sterologenesis is not only less sensitive to the cholesterol negative feedback system than that in the liver, but also is not subject to regulation by the bile acid negative feedback system.
D000818:Animals; D002784:Cholesterol / Q000494:pharmacology*; D002791:Cholesterol, Dietary; D002792:Cholestyramine Resin / Q000494:pharmacology*; D005215:Fasting; D005227:Fatty Acids / Q000096:biosynthesis; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity; D012737:Sex Factors; D013261:Sterols / Q000096:biosynthesis*
D002791:Cholesterol, Dietary; D005227:Fatty Acids; D013261:Sterols; D002792:Cholestyramine Resin; D002784:Cholesterol