LIPID STORAGE UNDER ABNORMAL CONDITIONS 639 



infiltration in the liver is related to the proportion of d 4 to Cis saturated 

 acids in the diet. Solid unsaturated fatty acids were shown to exert no 

 effect. On the other hand, elaidic acid was distributed normally, and ap- 

 peared in the liver in proportion to its amount in the diet. Choline, how- 

 ever, plays no role in the deposition of carcass fat. 867 



Another characteristic of fatty livers is the fact that, apparently, there is 

 a difference in susceptibility as related to species. Although mice, rats, 

 and dogs readily develop fatty livers on diets deficient in choline, Handler 568 

 observed that guinea pigs did not accumulate abnormal levels of liver fat on 

 these regimens. This fact can apparently be correlated with the lack of 

 hepatic choline oxidase activity in the guinea pig. 



Age plays a prominent role in the hepatic response to choline and cystine 

 deficiencies. Young rats succumb much more readily than do older rats 

 when these supplements are absent from the diet. While choline defi- 

 ciency almost invariably results in hepatic fibrosis in young rats, Handler 

 and Fallis 569 state that, in the case of rats eight months of age or older, 

 fatty livers alone result. Although the incidence of hepatic necrosis due to 

 cystine deficiency was found to be about the same in young and in old rats, 

 the rate of development was about three times as rapid in the former case. 



c. Conditions Related to the Development of Pathologic Fatty Livers. 

 Many factors will result in the development of pathologic fatty livers but, 

 for the most part, they are related either directly or indirectly to the base, 

 choline. Since this compound is the most important substance related to 

 fatty livers, both in the historical development and in more recent practical 

 application, it will be considered at length. 



(a) Choline and Choline Precursors as Lipotropic Agents, a'. The 

 Historical Development of Knowledge of the Lipotropic Action of Choline : 

 The realization that choline acts to prevent the accumulation of fats in the 

 liver is a direct outgrowth of the discovery of insulin. The first relatively 

 short-term experiments of Banting and Best on the maintenance of depan- 

 creatized dogs by means of insulin were signally successful in clarifying 

 diabetic conditions. However, it was noted simultaneously by Fisher 570 

 and by Allan, Bowie, MacLeod, and Robinson 571 that, when the operated 

 animals were maintained for periods up to two years on this hormone, the 

 dogs had large yellow livers containing an excess of fat. The development 



567 C. S. Raman, Biochem. J., 52, 320-324 (1952). 



568 P. Handler, Proc. Soc. Exptl. Biol. Med., 70, 70-73 (1949). 



669 P. Handler and R. H. Fallis, Jr., Proc. Soc. Exptl. Biol. Med., 75, 567-570 (1950). 

 870 n. F. Fisher, Am. J. Physiol., 67, 634-643 (1924). 



671 F. N. Allan, D. J. Bowie, J. J. R. MacLeod, and W. L. Robinson, Brit. J. Exptl. 

 Pathol, 5, 75-83 (1924). 



