Further observations on the lipotropic need for inositol.

Inositol was originally shown to be a lipotropic agent in rats maintained under special conditions (1) ; the animals were depleted of fat and of B vitamins by maintenance for 3 weeks on a fat-free, high carbohydrate diet, and during a subsequent week fat synthesis was promoted by a supplement of B vitamins and a beef liver fraction. Under these conditions the rats developed markedly fatty livers containing largeamounts of cholesterol. These fatty livers were produced despite the provision of choline, both in the liver fraction and as a supplement. The accumulation of fat and cholesterol in the liver was prevented by administration of inositol. The lipotropic action of inositol in rats has been confirmed by Engel (2), by Forbes (3), and by Handler (4), and has been demonstrated in humans by Abels et al. (5). Several explanations of the production of fatty livers resistant to choline but responsive to inositol have been offered. In early work in this laboratory, crude preparations of biotin appeared to be equivalent to the beef liver fraction in producing the effect; the term “biotin fatty liver” was used to describe the fatty liver responsive to inositol. Subsequent investigation with pure biotin showed that this concept was erroneous (6) ; the biotin explanation has been fully criticized by Best et al. (7). In several studies in our laboratory, attempts were made to define further the dietary conditions necessary to cause fatty livers characterized by a high cholesterol content (resulting from synthesis) and by resistance to choline. By means of the same basal regimen, it was found that, when thiamine was the only supplement, the fatty livers were completely responsive to choline (8). With the addition of the other B vitamins increasing resistance to choline and responsiveness to inositol were observed (8) ; the full effect was secured only when beef liver fraction was furnished (6). Handler (4) concluded that the beef liver fraction could be replaced by biotin plus folic acid and has also stated that the effect was due to a stimulation of food consumption. In this paper further efforts to explain the production of fatty livers showing resistance to choline and responsiveness to inositol are reported. While it was found that the beef liver fraction could be partially fractionated, further work along this line appeared to be unnecessary because of results obtained with pure substances.