That the energy-producing components of the diet have a role in promoting utilization of food protein and in protecting the integrity of body tissue in the adult animal is clear. But no one metabolic picture describes the response of an experimental animal to variations in food energy value since the protein metabolism is a function not only of the energy value of the diet but of other simultaneously operating factors.
Whether catabolism or anabolism predominates in the adult animal following caloric restriction depends on the degree to which the energy value of the diet has been reduced, the quantity and nutritive value of the dietary protein, the size and nature of labile body reserves in respect to protein, fat, and glycogen, and in some instances, dietary sources of energy.
There has been a renewed interest, of late, in the special roles played by carbohydrate and fat in the regulation of protein metabolism, as
appreciation of the interdependence of nutrients in nutrition has de-veloped. And, as is the case in regard to the total energy value of the diet, the response of the animal to either the dietary inclusion or omission of either nutrient reflects physiological, dietary, and environmental con-ditions.
In general, when normal adult animals are used in experiments of sufficiently long duration, carbohydrate and fats supplied in adequate mixed diets exert equivalent effects on the utilization of protein and the retention of nitrogen. They behave similarly also upon restriction of the energy value of the diet providing that the lipid content of the fat-con-taining diet is held within reasonable limits. This response has been called the nonspecific effect of calories upon nitrogen retention. But car-bohydrate may also exert a specific effect upon protein utilization as shown by feeding carbohydrate and fat simultaneously with, and apart from, the protein moiety of the ration.
However, carbohydrate and fat are not equally effective in the main-tenance of the endogenous nitrogen metabolism when a stress in the form of restricted food energy is imposed. Fat exerts a definite sparing effect as shown by decreased excretions of nitrogen in the urine and deferred death. Its protective influence is demonstrable in rats adapted to protein-free diets and fed rations of low energy value, either con-taining or devoid of fat.
As the caloric value of the diet is progressively decreased, the sig-nificant role played by dietary fat in reducing the rate of catabolism becomes apparent. The incorporation of fat in the ration prevents the marked increase in the quantity of nitrogen excreted in the urine that occurs when carbohydrate provides calories in one-half the needed amount. When fat is present, there are no increments in urinary nitrogen until the calories are restricted to one-fourth of the requirement, and then increases are of definitely lower order than they are when carbo-hydrate is the source of energy.
But, it is important to note that when the period of protein depriva-tion is prolonged without restricdepriva-tion of calories, fat loses its protective influence as measured by rate of catabolism and time of survival. Thus, the effectiveness of fat in sparing the endogenous metabolism appears to be a function of the amount of energy provided by the protein-deficient diet.
In regard to the efficiency of fat in sparing body protein, the quantity of fat present in the calorically-restricted diet is important. Lipid consti-tuents should represent at least 15% of the ration if the rapid catabolism associated with the feeding of low-fat, low-calorie rations is to be re-tarded.
FOOD ENERGY AND THE METABOLISM OF NITROGEN 2 2 1
Also, individual fats seem to possess the nitrogen-sparing properties in varying degree. Although all fats will retard nitrogen catabolism, solid fats seem to have a greater protective effect than the oils, especially in tests of long duration. In general it is believed that even though dietary fats and combinations of lipid components may differ in their effective-ness in depressing protein losses, the presence of fat per se seems to be of greater importance than structural characteristics. If any fraction of the fat molecule possesses greater activity than another, the nonsaponi-fiable portion in the case of pure cottonseed oil would be so designated.
The nature of the adaptation, associated with prolongation of life, of which the protein-depleted rat is capable when fed fat-containing diets of low caloric value is not clear at the present time. Since the fat-con-taining diet has been consumed or administered in quantities isocaloric with rations devoid of fat, it seems that its protective role must be described in terms other than the provision of calories in this instance.
This role undoubtedly bears an intimate relation to the physiological state of the animals used in the experiments, i.e., rats with greatly re-duced stores of labile body protein. Normally, enzymes represent a large part of the labile protein reserves in the liver (Miller, 1948). With de-pletion, concentrations of many tissue enzymes are altered so that im-balances in proportions of one to another arise (Allison, 1957). Also, there may be inhibition in the production or activity of vital hormones (Samuels, 1946).
The animal body has mechanisms of adaptation to wide variations in the intake of the three major foodstuffs (Samuels, 1946; Russell, 1957).
As a result, many adaptations have occurred before caloric restriction is initiated. Thus, the fat-fed rat may enter the period of caloric stress with a body better equipped to handle the emergency than does the carbo-hydrate-fed rat. Preliminary experiments suggest that dietary fat pre-vents the increase in cytochrome oxidase activity that has been associated with an absence of fat in the diet (Swanson and Artom, 1950; Kunkel and Williams, 1951) and with inadequate protein (Allison, 1957).
How then in this experimental situation does fat function in retarding body breakdown? At this point, we can only conjecture. In some way, the fat component of the diet seems to confer economy of utilization of food energy. It may be significant that utilization of carbohydrate is approximately normal in rats fed fat in diets that meet the energy needs.
Closely associated is the observation that dietary fat promotes the trans-formation of intermediate nitrogenous catabolites to urea and eliminates in large part the necessity for excretion of some of these intermediates as ammonium compounds.
The nature of the carbohydrate metabolism is being explored further
in experiments in which the rate of acetate-2-C14 oxidation is being de-termined under the various experimental conditions.
As adaptive processes shift in the deficient rats with the prolongation of the experimental interval, certain fats prevent further increases in the excretion of urine nitrogen. This observation suggests that either the fat itself, or a component grouping, or some associated material, i.e., sterols, may have a place in the regulation of metabolic events, by serving as precursor material for the synthesis of important body metabolites or enzymes or hormones. Or if dietary fat does not participate directly in the manufacture of such substances, it may augment or support the work of some enzyme produced perhaps in suboptimal amounts, insulin for example. As a result, new pathways for handling intermediate catabolic products may be established.
Again, the fact that methionine when added to the low-fat, low-calorie diets affects the general course of nitrogen catabolism in the same way as fat suggests that control of the lipid metabolism may be the crucial factor. A need for precursor substances for the synthesis of phospholipids may have been created by the triple stress condition, with fat and methionine each capable of supplying the critical intermediate(s).
Thus far, the data describing the role of fat in the metabolism of the protein-deficient rat, fed food of restricted energy value, are largely descriptive. We have been attempting to portray the complete picture.
Only, when we have adequate information about the various facets of the phenomena, can we explain the various adaptive changes observed in the endogenous metabolism. Suffice to say that probably the protein, carbohydrate, and fat metabolisms all are implicated. What the inter-relationships may be will give insight into the adaptations of which the organism is capable under the conditions of stress to which these par-ticular animals were exposed.
ACKNOWLEDGMENTS
The studies reported from the Nutrition Laboratories of the Home Economics Research Department of the Iowa Agricultural and Home Economics Experiment Station were conducted in collaboration with Mrs. Wanda Willman Smith, Dr.
Miriam Brush, Dr. Gladys Stevenson, Dr. Hazel Fox, Dr. Cecile Hoover Edwards, and Dr. Lotte Arnrich. I am indebted to them for the use of certain hitherto un-published experiments that are included in this chapter.
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