X. EFFECTS OF DEFICIENCY 81 



by inositol. Best et al. have reinvestigated the hpotropic activity of inositol 

 and have found that the analysis for liver lipids at the end of the 7-day test 

 subsequent to the depletion period may not be representative of values 

 existing earlier or later. ^^ They concluded that inositol has no unique lipo- 

 tropic properties and that it is inferior to choline in the reduction of either 

 liver fat or cholesterol esters. Its supplementary action with choline in fat- 

 free diets was confirmed. No explanation has been brought forward for the 

 influence of inositol on liver lipids other than its possible role in an inositol- 

 containing phospholipid. 



In 1933 Blatherwick ei al. reported the occurrence of fatty livers in rats 

 fed large amounts of whole liver.^®^ This result was confirmed by Beeston 

 and Wilkinson, who were unable to demonstrate a lipotropic action of 

 choline. ^^^ McHenry, using the depletion procedure referred to above, found 

 marked increases in liver fat and cholesterol following the feeding of a liver 

 fraction"" and biotin.^'^'^' ^^^ The term "biotin fatty liver" was applied, and 

 it was believed that inositol was more effective than choline in this condi- 

 tion. The concept of a special type of fatty liver due to l)iotin was attacked 

 by Best ct al.}'^^ and by Handler.^^^ These workers were unable to find satis- 

 factory evidence for an unusual effect of inositol or for a special role of biotin 

 other than the effect to be expected as a result of changes in food intake and 

 utilization. 



McHenry noted a marked increase in liver fat in rats following the addi- 

 tion of thiamine to a low choline, thiamine-deficient diet."- Choline, but 

 not inositol, was found to l)e lipotropic for this so-called "thiamine fatty 

 liver." Somewhat similar results Avere observed by Engel and Phillips, who 

 concluded that thiamine therapy caused a temporary pathological state as 

 a result of disruption of cells by excessive production of fat."^ The hydropic 

 degeneration and fatty changes were not prevented by choline, but des- 

 iccated thyroid was effective. McHenry had suggested earlier that thiamine 

 might be essential for the synthesis of fat from carbohydrate."^ The proba- 

 bility of such an origin of the extra liver lipids in choline deficiency was 

 supported by the exclusion of increased absorption from the intestine"^ and 

 of increased mobilization of tissue fat^^ as possible sources. Regardless of 



168 N. R. Blatherwick, E. M. Medlar, P. J. Bradshaw, A. L. Post, and S. D. Sawyer, 



J. Biol. Chem. 103, 93 (1933). ^ 



i«3 A. W. Beeston and H. Wilkinson, Biochcm. J. 30, 121 (1936). 

 '^0 E. W. McHenry and G. Gavin, Science 91, 171 (1940). 

 '^' C. H. Best, C. C. Lucas, J. M. Patterson, and J. H. Ridout, Biochem. J. 40, 368 



(1946). 

 '^2 E. W. McHenry, /. Physiol. {London) 89, 287 (1937). 

 1" R. W. Engel and P. H. Phillips, J. Nutrition 18, 329 (1939). 

 '•'^ E. W. McHenry, Science 86, 200 (1937). 

 •" H. E. Longenecker, G. Gavin, and K. W. McHenry, J. Biol. Chem. 134, 693 (1940). 



