RELATION OF THE IODINE VALUES OF MESEN-

Transcription

1 FATTY ACID METABOLISM IN THE LIVER. IV. THE RELATION OF THE IODINE VALUES OF MESEN- TERIC AND KIDNEY FATTY ACIDS TO THOSE OF LIVER FATTY ACIDS IN PREGNANT AND LAC- TATING RABBITS. By R. COOPE AND V. H. MOTTRAM. IN a research on fatty infiltration of the liver during late pregnancy and early lactation(l) a number of observations were made on the iodine values of the fatty acids from the mesentery, the liver and the kidney, in the expectation that these iodine values would give evidence confirmatory of an infiltration. It was assumed that the iodine values of the fatty acids of the fat d6p6ts (from the subcutaneous tissue, the mesentery and around the kidney) would approximate to constancy with a mean of 64-4(2), and that, further, the iodine values of the fatty acids of the normal liver would be about (s). If any transport of d6p6t fats from the d6p6t to the liver were to occur in amount sufficient to mask the desaturating influence of the liver(4) it would show itself not only as an increase in the mass of fat present, but as a decrease in the iodine value of the liver fatty acids(s). This process has frequently been observed at work in research on fat metabolism(6), and where the infiltrations are large and rapid7), an increase in the fatty acids in the liver corresponds with a decrease in their iodine value. It is obvious that this effect would be more demonstrable the larger the infiltrations, the lower the iodine value of the ddp6t fatty acids, the more sluggish the liver and the more constant the iodine values of the dep6t fatty acid. In earlier work it was assumed that this last desideratum was attained by placing animals, in which the fat ddp6ts had been depleted, for a long time (five months) on a constant liberal diet, so thlat the nature of the fat in the fat d6p6ts was determined by the nature of the food. This assumption may yet prove to be justified; but in any case direct estimations of the iodine values of the d6p6t fatty acids -were desirable and so, in this research, have always been made. They give us a measure of the lower level from which the animal organism proceeds to desaturate the fat(s). Protocols of the experiments made are to be found in the previous article(l).

2 158 R. COOPE AND V. H. MOTTRAM. A reference to the table of results will show that in the animals investigated the variation of the iodine value of the fatty acids of the fat d6p6ts from the mean is great. A similar variation, where constancy was expected, was observed by one of us in the iodine value of the fatty acids from the egg of the domestic fowl(g). In the present case it is from 60 to 90 approximately, with a mean of 76x1 and a standard deviation of This standard deviation expressed as a percentage is + 10O85. In other words, the variation of the nature of the fatty acids of the fat d6p6ts of animals treated alike as regards dieting and environment for at least a month, is so great as to render all argument based on the assumption of their constancy absurd. Further, the assumption that the triglycerides found in the fat de6pots of domesticated herbivores are of the nature of oleo-stearo-palmitins is seen not to be justified; animals fed on oil cakes containing unsaturated oils of the cotton seed oil type being of course excluded. The fatty acids obtained were solid at room temperature, yet one sample had an iodine value almost identical with theoretical value for oleic acid (90-07). Consequently it is probable that acids of the linoleic or perhaps more desaturated series are present. The failure of the ddp6t fatty acids to achieve constancy necessitated the collection of other data. The lower level from which desaturation proceeds being determined, we estimated the upper level to which it moves. This, we assume, we have in the iodine value of the fatty acids from the kidney substance. From the kidneys the capsule was first removed, and then all visible fat deposited on the neck of the ureter, around the calyces and blood vessels dissected away. The remaining tissue was dissolved in potash in the usual way, and the iodine value of the pure non-volatile fatty acids estimated by substantially the same method as that described by one of us earlier(s). In the seven cases examined there was a variation between 114,1 and 122-3, with a mean of and a standard deviation of This deviation expressed as a percentage is Such a deviation, in view of the difficulties of estimation, is surprisingly low, for it is within the range found for parallel estimations on ten grammes of fresh liver and is only a little above the mean of those standard deviations (± 1-54)(3). In other words the results are as constant as the method used would lead us to expect, and if we may argue from seven estimations on different animals, they show that the desaturation of fatty acids for use in the kidneys proceeds to a constant definite level. A similar constancy in the iodine value of the fatty acids of a tissue

3 FATTY ACID METABOLISM. uncontaminated with d6pot fat has been observed by one of us in the myotomes of the plaice(io). There, in a set of 13 estimations still more difficult, the standard deviation of iodine values expressed as a percentage is We have, therefore, some justification in assuming that when an organism desaturates fatty acid for use in its tissues, it does so to a degree constant for the species and the organ. If this be so, we have two points fixed between which, in animals treated as those investigated were treated (viz. for at least one month on Control rabbits. Exp. 9 Mesentery 89:73 (a) ( (a) i 83'08} (a) ' '6 Pregnant or lactating rabbits. (a) (b) (c) TABLE I. Iodine value of fatty acids Liver(b) Kidney 111'8 109' '3J 106' ) a,5. ~(117)(c) 106'0] 106' J 95'28 92'92 94' '10J 109 (117)(C) 15 64*36 64J36 (a)63'8 ~88'82~ '27 92'08J ' ' ' '7 (117)(c) 18 69:58 (a) 68' ) 103 (117)(c) 91' '8 92' (117)(C) ' '8 101i0J 118 Parallel estimations on the same sample of fatty acids. Parallel estimations on aliquot portions of fresh liver. Mean value of estimations on kidneys of remaining animals. 159

4 160 R. COOPE AND V. H. MOTTRAM. atnple dietary in separate cages), the iodine values of the fatty acids of the liver should range, if Leathes' interpretation of the role of the liver in fatty acid metabolism be true. It will be seen from Table I that in every case quoted this is so. One exception only have we met, and in that experiment we could not, unfortunately, confirm the result, as sufficient material for a second estimation was not available. It occurred early in our work, and we think it justifiable to discard the estimation, as due to a mistake in technique. In no subsequent estimations have we had reason to doubt any results, for whenever duplicates were made the results are within the range of experimental error. Finally, we can proceed to argue from the position at which the liver fatty acid iodine value is interpolated between d6pot fatty acid iodine value and kidney fatty acid iodine value, to an infiltration of the liver with d6p6t fatty acids. We can find the average distance of liver fatty acid iodine value between the two limits of its variationddp6t fatty acid and kidney fatty acid-and compare it with the average distance in the cases of livers suspected of being infiltrated. It is true that we have a complicating variable of unknown dimensions in the desaturating action of the liver on the fatty acids sent to it from the dep6ts. Imrie(s) has shown reason to believe that this action is obvious when the grade of infiltration is low-exactly the cases with which we are dealing(i). But this activity of the liver would militate against the magnitude of the difference we might expect to observe. If, then, in spite of this, we discover a difference, the argument becomes so much the stronger. And we can discover such a difference. TABLE II. Control rabbits. Exp. di Ch d. dl Mean 0 65 Pregnant or lactating rabbits * Mean 0-56

5 FATTY ACID METABOLISM. In Table II the difference between the iodine values of fatty acids of the mesentery and of the kidney is given in Column I, and is represented as dl. In Column II is given the difference between the iodine values of the fatty acids of the mesentery and of the liver, and this we represent as d,. Column III (d2 + dl), gives a measure of the distance between the two limiting values at which we find the iodine values of the liver fatty acids. In control animals (Exps. 9-14) the average value is 0'65, in pregnant and lactating animals (Exps ) the average value is In other words, the iodine value is nearer that of the dep6ts in animals at or about the time of parturition than it is in normal animals. The liver is infiltrated with d6p6t fatty acids. SUMMARY. 161 Rabbits, even when carefully treated to obviate metabolic abnormalities, show wide variations in the iodine values of the fatty acids from mesenteric fat. But the iodine values of the fatty acids from kidney tissue (seven experiments) show a marked constancy. In between these limits, as we should expect, lie the iodine values of the liver fatty acids. In animals, at or about the time of parturition, the iodine values of the liver fatty acids lie nearer those of the mesenteric fatty acids than in normal control animals: evidence of an infiltration of the liver (confirming the conclusions of the previous paper) with d6p6t fatty acids. The expenses of this research were mainly defrayed by a grant from the Royal Society. REFERENCES. (1) C oope and Mott ram. This Journal, xmxa. p (2) Lewkowitsch. Chem. Technology and Anal. of oils, fats and waxes. 5th ed. p (3) Mottram. This Journal, xr. p (4) L e a th es. Lancet, 1909, p (5) Imrie. Journ. of Path. and Bact. xix. p (6) Hartley and Mavrogordato. Journ. of Path. and Bact. xii. p (7) Mo ttram. This Journal, xxxviii. p (8) Hartley. This Journal, xxxvi. p. xvii. 1907; xxxvin. p Also Leathes. (9) Mottram. Proc. Physiol. Soc. p. xviii This Journal, XLVII. (10) Mottram. This Journal, XLV. p