392 VIII. CHOLESTEROL AND RELATED STEROLS 



As regards the first category, Langdon and Bloch-^^ reported that choles- 

 terol synthesis from acetate was inhibited in the liver of the rat, not only 

 by cholesterol, but also as a result of the feeding of squalene, A'^-cholestenol, 

 and 7-dehydrocholesterol ; the reduction in rate was accompanied in each 

 case by a significant increase in liver cholesterol. Tomkins, Sheppard, and 

 Chaikoff"'"' likewise noted that the administration to rats of cholestenone, 

 dehydroisoandrosterone, 7-dehydrocholesterol and A'^-cholestenol, in a 

 single dose or in daily doses over five to seven days, markedly reduced the 

 rate of the acetate —*■ cholesterol reaction in the liver, without affecting the 

 rate of C'^02 production. The effect of phytosterols and of related com- 

 pounds, which block cholesterol absorption, is discussed in f . 



e. The Effect of Fat Feeding. It has been postulated not only that 

 animal fats, which contain cholesterol per se, are a source of this sterol in 

 the animal, but also that vegetable fats provide cholesterol because the 

 acetate molecules are available as a result of the oxidation of fatty acids. 

 In fact, Lifschiitz^^^ reported that an oxidized product of oleic acid gave 

 some of the reactions of the sterols. Minovici^'*'- noted an increase in the 

 cholesterol content of the blood of dogs when oleic acid was given. Eck- 

 stein and TreadwelP^^ also observed that greater amounts of sterols were 

 present in the livers of growing white rats when the percentages of corn or of 

 soybean oil in their diets were increased. The latter workers are of the 

 opinion that this result cannot be ascribed to a sterol mobihzation. On 

 the other hand, several groups of investigators^^*--^^-*^ failed to confirm a 

 relationship between fat intake and the rate of cholesterol synthesis. 

 Thus, Schoenheimer and Breusch^^'* were unable to demonstrate any in- 

 creased cholesterol synthesis in mice which were fed considerable amounts 

 of lard and of other fats. Similar results were observed by Alfin-Slater 

 et al.^^^ on rats. The latter workers found no change in the amount of 

 cholesterol in the liver and plasma when a low-fat diet was replaced by a 

 high -fat regimen. In the case of rats which had a high liver cholesterol 

 level as a result of prefeeding with this sterol, it was found that the high-fat 

 diet was more efficient in removing from the liver the cholesterol which had 

 accumulated than was a low-fat regimen. However, Hildreth et al^^^ 



2« G. M. Tomkins, H. Sheppard, and I. L. Chaikoff, /. Biol. Chem., 203, 781-786 

 (1953). 



2" I. Lifschiitz, Z. physiol. Chem., 55, 1-7 (1908). 



2« S. Minovici, Bull. soc. chim. bioL, 17, 369-395 (1935). 



=*" H. C. Eckstein and C. R. Treadwell, J. Biol. Chem., 112, 373-378 (1935-1936). 



2^4 J. M. R. Beveridge and S. E. Johnson, Brit. J. Exptl. Pathol, 31, 294-305 (1950). 



2« E. A. Hildreth, S. M. MeUinkoff, G. W. Blair, and D. M. Hildreth, Circulation, 3, 

 641-646 (1951). 



