Fats 19 



There is, however, another explanation that deserves attention. 

 This arose out of claims that the amount of fat that can be extracted 

 from fatty organs, especially the kidneys, is about the same as that 

 in the normal organ, even though the microscope suggests other- 

 wise. Wells (1925) , for instance, found a mere 16 per cent fat in a 

 kidney that looked extremely fatty to the naked eye; the fat content 

 of the normal organ is about 18 per cent. The only way out of this 

 dilemma is to suggest that fat may be liberated or "unmasked" in 

 damaged cells and so lose its close union with other components. 

 These, quite likely, are proteins. Much of the "masked" fat resists 

 calls made on it during starvation, and it cannot be extracted by 

 solvents such as ether. Quite a large part of this lipid is lecithin, 

 cholesterol and their esters. Deliberate digestion by enzymes is 

 needed if the invisible fat is to be set free so as to show up as "fatty 

 degeneration." 



But this plausible theory has received a series of hard knocks 

 in recent years from the quantitative studies of Dible and his co- 

 workers and now most of us prefer the infiltration theory as the 

 explanation of fatty change. However, a fresh impetus has come 

 from a totally unexpected direction, for our ideas about the nature 

 of fatty change were largely revolutionised when Banting and Best 

 discovered insulin in 1922. Soon afterwards it was noticed that a dog 

 deprived of its pancreas but kept alive with insulin develops a fatty 

 liver which in time can prove fatal. Feeding the animal raw pan- 

 creas prevents this mishap. Subsequent investigation showed that 

 lecithin, and especially choline, which is an important part of the 

 'lecithin molecule, is the effective lipotropic agent (Best and Hunts- 

 man, 1932) . The Canadian ivorkers also discovered that the liver 

 accumulates fat when rats are fed mixed grains and fat. This, too, 

 can be prevented by adding lecithin or choline to the diet. Such 

 studies culminated in the idea of the lipotropic action of protein, 

 cystine and methionine and led to the suggestion by du Vigneaud 

 of transmethylation or transfer of methyl groups. By labelling com- 

 pounds with isotopes he showed that methyl groups interchange 

 between methionine, creatine and choline, when either one or 

 other is deficient, in an endeavour to synthesise the missing sub- 

 stance. Many donors of labile methyl groups have since been 



