Formation of Fatty Acids 281 



substrates or precursors into the fatty acids is almost entirely abolished 

 or very materially decreased in the alloxan- treated animal. 



The livers of cats do not incorporate acetate into fatty acids so well 

 as those of rats; nevertheless, there is a fair amount of incorporation 

 (Table III). Fasting does not seem to influence the incorporation of 

 acetate into long chain fatty acids as it does with glucose. You will 

 remember that Chaikoff found that livers from diabetic animals are 

 unable to convert glucose into fat; fasting also had the same influence. 

 There seems to be some block in the conversion of glucose to fat in the 

 livers of such animals, whereas with acetate in our experiments there 

 seems to be no such block. Taking livers from depancreatized cats — 

 we are happy we did as Chaikoff' s recent work shows profound differ- 

 ences between alloxan-treated and depancreatized animals — we again 

 found a marked diminution in the ability of liver slices from such cats 

 to synthesize long chain fatty acids from acetate. 



We also had occasion through the co-operation of Dr. Francis Lukens 

 to study livers from Houssay-animals, rats from which the pancreas 

 and hypophysis have been removed, and we find that in these the liver 

 has had restored to it the ability to convert acetate into long chain fatty 

 acids. 



We have since then carried out a few preliminary experiments in 

 which we have injected purified growth hormone into Houssay-animals, 

 and once again that inhibits the liver's ability to incorporate acetate 

 into long chain fatty acids. 



It would thus appear, at the moment, that liver slices are able to 

 synthesize fat in the absence of both pancreas and the pituitary and 

 that the pituitary secretes a principle — perhaps more than one — which is 

 capable of inhibiting the biosynthesis of fat from acetate. We picture, 

 this whole process as being a competition or antagonism between the 

 pancreas and the pituitary, and we think that this is significant to our 

 understanding of diabetes, where the conversion of carbohydrate to 

 fat appears to be such an important process. One is struck by the 

 similarity between this and the hexokinase story. We feel confident 

 about this work because it not only occurs in different species, but also 

 because the magnitude of the effects is very great. 



Block: When Kramer and I described the insulin effect upon fatty 

 acid synthesis in vitro four years ago, we were struck by the finding 

 that when acetate was the labelled substrate this effect could be 

 demonstrated only in the presence of pyruvate. In the presence of 

 acetate alone the insulin effect was not demonstrable, in contrast to 

 what Dr. Gurin finds. One of the factors which is responsible for these 

 differences may have to do with the rat strains used. The storage of 

 endogenous metabolites in surviving liver is probably quite variable. 

 A hormonal effect may merely reflect the adequacy or deficiency of 

 endogenous material which provides the energy for fatty acid synthesis. 

 I believe that as yet there is no evidence that insulin exerts a specific 

 effect on fat synthesis. What has been observed can be attributed to 

 the intervention of insulin in energy yielding reactions of carbohydrate 

 metabolism. 



