Nonisotopic Method for Estimating Cholesterogenesis in the Rat
Influence of several compounds on sterol production was determined from serum desmosterol (D) levels in rats treated with U-18666A:3β-(2-diethylaminoethoxy)androst-5-en-17-one HCl. U-18666A blocks biosynthesis of cholesterol (C) by inhibiting conversion from D to C. Diets containing C (2%), the bile acid sequestrant colestipol HCl (1%), clofibrate (0.2%), combination of colestipol HCl and clofibrate, or basal diet were fed to normal or U-18666A (3 mg/kg/d) male rats for 2 weeks. In normal rats, C feeding increased serum C levels (39%), colestipol HCl had no significant effect, while clofibrate or the combination with colestipol HCl reduced C levels to the same extent (37%). In U-18666A-treated rats, C feeding reduced D concentration (30 to 13 mg/dl) indicating inhibition of synthesis via negative feedback system. Colestipol HCl increased D level (33%) and reduced C (60%) indicating increased synthesis; results are compatible with an agent capable of binding bile acids in the rat which can compensate for loss of these acids by increasing sterol synthesis. Compared to control, clofibrate reduced serum C (33%) and D (43%); in combination with colestipol HCl it inhibited the increased synthesis caused by the latter. Clofibrate appears to be an inhibitor of C biosynthesis. Also, tests with other compounds make it apparent that the U-18666A-treated rat model system can be useful in evaluating cholesterogenesis.
KeywordsBile Acid Serum Cholesterol Basal Diet Normal Animal Cholesterol Biosynthesis
Unable to display preview. Download preview PDF.
- 2.Dvornik, D., M.L. Giver, and J.G. Rochefort. 1965. AY-9944, an inhibitor of cholesterol biosynthesis, as tool in the estimation of the rate of cholesterogenesis. Circulation 32: Suppl. II, 10–11.Google Scholar
- 3.Giver, M.L., J.G. Rochefort, and D.M. Dvornik. 1966. Tool for the estimation of the rate of cholesterol biosynthesis. Circulation 34:Suppl. III, 12.Google Scholar
- 8.Abell, L.L., B.B. Levy, B.B. Brodie, and F.E. Kendall. 1953. A simplified method for the estimation of total cholesterol in serum and demonstration of its specificity. J. Biol. Chem. 195:357–366.Google Scholar
- 9.Snedecor, G.S., and W.G. Cochran. 1967. Statistical Methods, The Iowa State University Press, Ames, Iowa. pp. 258.Google Scholar
- 14.W.A. Phillips. 1971. Studies with known hypocholestermic agents in U-21743 (p-chlorophenyl methanesulfonate)-induced hyperlipidemic rats. Fed. Proc. 30:369.Google Scholar
- 15.Phillips, W.A. and G.L. Elfring. Effect of U-21743 (p-chlorophenyl methanesulfonate) on cholesterol turnover in the rat (in preparation).Google Scholar
- 17.Gould, R.G., E.A. Swyryd, D. Avoy, and D.M. Coan. 1967. The effects of α-p-chlorophenoxyisobutyrate on the synthesis and release into plasma lipoproteins in rats. Prog. Biochem. Pharmacol. 2:345–357.Google Scholar
- 18.Hill, P. and D. Dvornik. 1971. Agents affecting lipid metabolism. XL. Effect of ethyl chlorophenoxyisobutyrate on liver lipids and serum lipoproteins in rats. Can. J. Biochem. 49:903–910.Google Scholar
- 21.Cayen, M.N. and D. Dvornik. 1970. Agents affecting lipid metabolism. XXXIX. Effect of combined administration of ethyl chlorophenoxyisobutyrate and cholestyramine on cholesterol biosynthesis in the rat. Can. J. Biochem. 48:1022–1023.Google Scholar
- 22.Duncan, C.H. and M.M. Best. 1960. Lack of nicotinic acid effect on cholesterol metabolism of the rat. J. Lipid Res. 1: 159–163.Google Scholar