100 CHOLINE 



fat content of human bone marrow was decreased markedly following the 

 intravenous administration of choline. ^^^ 



Interest in choline as an anti-fatty liver factor originated with the first 

 experiments designed to test w^hether the administration of insulin was 

 sufficient to replace the internal secretion of the pancreas in depancreatized 

 dogs.^^^' *^^ The manner in which these studies led to the recognition of the 

 lipotropic activity of choline has been described in Section IV, p. 19. In 193G 

 Dragstedt and coworkers published the first of a series of papers on lipocaic, 

 a factor believed to be a true hormonal product of the pancreas and in- 

 volved in lipid metabolism in the liver .-^-' ^76-379 Fatty infiltration and de- 

 generation, the hepatic changes in depancreatized dogs, were not observed 

 in animals after ligation of the pancreatic ducts or after preparation of total 

 pancreatic fistulae. Pancreatic juice was ineffective, if administered orally. 

 Choline was not believed to be the main protective agent because the po- 

 tency of raw pancreas was considered much greater than its content of 

 choline. For these reasons Dragstedt concluded that the external digestive 

 secretion of the pancreas was not an important factor. This latter finding 

 has not been confirmed. Ralli et al. were unable to find any difference be- 

 tween the fatty changes in the livers of dogs after pancreatectomy and 

 after ligation of the ducts,^^° and Best and Ridout could find no satisfactory 

 evidence for lipocaic as a second pancreatic horaione.^^^ This problem was 

 reinvestigated by Chaikoff and coworkers, who arrived at the following 

 conclusions : (a) a fraction can be prepared from the pancreas which is more 

 protective than can be accounted for on the basis of its content of choline, 

 although sufficient choline is as effective as the pancreatic fraction;^*' (b) 

 ligation of the ducts does result in a fatty liver, and the liver changes are 

 prevented by the oral administration of pancreatic juice ;^^- (c) the fatty 



"3 F. B. Moosnick, E. M. Schleicher, and W. E. Peterson, /. Clin. Invest. 24, 228 



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Pathol. 5, 75 (1924). 

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175 (1936). 

 "' W. C. Goodpasture, C. W. Vermeulen, P. B. Donovan, and L. R. Dragstedt, Arti. 



J. Physiol. 124, 642 (1938). 

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