The Possibility of Gluconeogenesis from Fat

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Abstract
Respiratory metabolism studies on seven different subjects taking high-fat diets, following meals containing varying amounts of butter fat, show many respiratory quotients below the theoretical level for oxidation of fat. The occurrence of these low quotients does not depend upon the amount of fat taken in the experimental meal, nor upon the F.A.:G ratio of the general diet, so much as upon the tolerance of the subject. Adaptation to or tolerance of high fat in the sense of better capacity to oxidize fat and producing less ketosis may be acquired and be retained for several months. The level of the respiratory quotient bears no intimate relationship to the demonstrable ketosis or ketonuria. The hypothesis with which the work was undertaken, calling for a special sequence of low quotients soon after the test meal followed by higher quotients later, has been realized in a number of individual experiments, but not in all. The most successful from this point of view are the early experiments for each subject performed before increased tolerance had developed. Low quotients may be induced to appear also by shivering at a time when, ordinarily, they would be high. Production of glycogen from the protein metabolism could account for a depression of the R.Q. at most of .025; while production of glycogen from glycerol, assuming that only the glycerol of the fat metabolism were available, would produce a depression of not more than .003. Correction of the quotient for the demonstrable ketosis and consequent ammonia formation would not account for more than .005. At most the combined effect of all these factors would not account for quotients lower than 0.69. The formation of glycogen from fat (beyond the amount which could arise from glycerol) having never been proved, it would be premature to conclude that the quotients below 0.69 in this work demonstrate gluconeogenesis from fatty acids. It is suggested, as an alternative explanation, that in the oxidation of fatty acid chains the uptake of oxygen may considerably outrun for a time the production of carbon dioxide and thus account for a depression of the R.Q. A process of desaturation which would remove hydrogen, but not produce any carbon dioxide, followed by oxidation with production of CO2, would fulfil the requirements.