74 CHOLINE 



The lipotropic effect in rats of exposure to cold constitutes a striking 

 exception to the usual correlation between severity of choline deficiency 

 and the metabolic level. Sellars and You found an average liver fat of 7.2 

 ± 1.24% in animals maintained at 2.5° whereas controls fed the same low 

 choline diet and maintained at 25° had an average liver fat of 24.8 ± 4.90 %. 

 The "cold" animals consumed 50% more food.^^ The choline-like effect of 

 cold was not a temporary phenomenon and continued through a 15-week 

 experimental period; it occurred in animals acclimatized to cold prior to 

 the feeding of the hypolipotropic diet; and it was not prevented by thyroid- 

 ectomy and subsequent administration of a daily maintenance dose of 

 thyroxin. ^^ However, exposure to cold was only partially lipotropic if the 

 diet contained 50 % fat. Stimulation of the adrenals was not believed a 

 primary factor because cortisone failed to prevent the development of the 

 fatty liver in rats on a low choline diet.^° The study of the increased metabo- 

 lism in "cold" rats under various conditions has not permitted a satisfactory 

 explanation of the lipotropism due to the lowered environmental tempera- 

 ture.^^ Although both thyroid and adrenal hormones were believed necessary 

 for the mechanism involved, hyperactivity of either gland was not con- 

 sidered an essential factor. ^^' ^'"' 



The administration of low molecular weight halogenated hydrocarbons 

 by injection or by inhalation in rats on low choline, low protein diets causes 

 severe fatty infiltration and degeneration of the liver. Heppel et al. found 

 methionine considerably more protective than choline, although the latter 

 with cystine increased the resistance of animals exposed to ethylene and 

 propylene dichloride.^"^- ^"^ Calder concluded that choline plus a thermo- 

 labile factor in yeast, which was not thiamine, decreased the liver damage 

 caused by chloroform in rats.^"' Carbon tetrachloride caused anemia as well 

 as hepatic pathology in rats.^"^ The former responded to methionine, but 

 neither methionine nor choline prevented the fatty degeneration. Coulson 

 and Brazda tested pyridine, quinoline, and a number of pyridine deriva- 

 tives and found choline relatively ineffective as a protective agent. ^"^ 



Reference has been made previously to the degenerative changes in the 



3« E. A. Sellers and R. W. You, Science 110, 713 (1949). 



" E. A. Sellers and R. W. You, Biochem. J., 51, 573 (1952). 



9*E. A. Sellers and S. S. You, Am. J. Physiol. 163, 81 (1950). 



'9 E. A. Sellers, S. S. You, and N. Thomas, Am. J. Physiol. 165, 481 (1951). 

 i"" E. A. Sellers and R. W. You, /. Nutrition 44, 513 (1951). 



loi L. A. Heppel, P. A. Neal, F. S. Daft, K. M. Endicott, M. L. Orr, and V. T. Porter- 

 field, /. Ind. Hyg. Toxicol. 27, 15 (1945). 

 '«2 L. A. Heppel, B. Highman, and V. T. Porterfield, J. Pharmacol. 87, 11 (1946). 

 los R. M. Calder, J. Pathol. Bacteriol. 54, 355 (1942). 



10* H. Benard and M. Gajdos-Torok, Com-pt. rend. soc. biol. 141, 122 (1947). 

 •"SR. A. Coulson and F. G. Brazda, Proc. Soc. Exptl. Biol. Med. 66, 1 (1947); 69, 

 480 (1948). 



