Fat-deficiency disease of rats. The effect of doses of methyl arachidonate and linoleate on fat metabolism, with a note on the estimation of arachidonic acid.

A HIGHLy unsaturated acid containing 20 carbon atoms and four double bonds was isolated by Hartley [1909] from the fatty acids of the. pig's liver as its octabromide and named by him arachidonic acid. Subsequently the same acid was shown by Levene & Rolf [1922] to occur as a constituent of lecithin and kephalin, and since that time it has been shown to be widely distributed in animal tissues. In the ox, it was identified among the fatty acids of the liver, both in the neutral fat and in the phospholipin fraction; it occurs also in the acids from the fat depots and in the phospholipins of the heart, spleen and adrenals [Klenk & v. Schoenebeck, 1932], whilst Klenk & Dittmar [1936] and Wesson [1924] identified it among the brain fatty acids. Wesson [1925] estimated its proportion in the various tissues and endeavoured to determine the part played by this acid in metabolic processes. Burr & Burr [1930] showed that the presence of highly unsaturated acids was essential for normal growth in rats and that these acids were not synthesized in the animal organism but had to be supplied in the diet. They found that either linoleic or linolenic acid could provide the missing factor, and that when either of these was included in the diet, normal growth was resumed. Wesson [1925] in his experiments had used corn starch as a constituent of the fatdeficient diet: this however on hydrolysis with acids yields appreciable quantities of linoleic acid [Taylor & Nelson, 1920] so that the essential fatty acid was actually being included in the diet of these fat-starved rats. It was also then not khown how very slowly the body is depleted of the essential acids and that only very long-continued experiments will produce the symptoms of fat deficiency. Burr et al. [1932] replaced 10% of a mixture of linoleate and linolenate by arachidonate and found that the relative increase of weight of rats receiving this mixture diminished when compared with rats receiving the full linoleate and linolenate supplements. It is however probable that the effect of a 10% substitution would give results within the biological variation of the experiment. Turpeinen [1938] found methyl arachidonate to be three times as potent in producing weight increase as methyl linoleate; he did not specifically describe its effect on skin symptoms in the different rats but, speaking generally, said that the skin symptoms met with in the laboratory were mild. He measured however the nunjber of ovulation cycles and found these to be markedly less than normal in the fat-starved rats but to be increased when arachidonate or