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* Address correspondence to Harry J. Mersmann. E-mail: mersmann{at}msn.com.
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ABSTRACT |
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 TOP ABSTRACT LITERATURE CITED |
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Blessed is he who maketh due proofe.
With due proofe and with discreet assaye
Wise men may learn new things every day.
–T. Norton, 1493
Thousands of animal experiments have contributed to the development of current energetics concepts. This article emphasizes these experiments, the powerful intellects behind them, and a few of the missteps along the way. The path of experimentation and conceptual development leads from the breath of life, through life as combustion, intensity of metabolic burn rates vs. body size, organ energy use, and recently to biological mechanisms controlling the flame. Parallel animal experimentation follows the valuation of foods and nutrients to fuel these flames.
In the introduction of The Science of Nutrition published in 1928 (1), Lusk apologizes to "all whose claims of priority of discovery have not been duly recognized. The overwhelming mass of the literature makes this a problem of increasing difficulty." What might be said today!
Breathing, life, and combustion
The realization of the necessity of breath and thus air for life of animals and man certainly predates recorded history. Early recorded notions from the 2nd century AD Greek physician, Galenos, proposed "pneuma xotikon" to be a vital spirit in air and predicted that indeed someday the substance would be isolated from air (2). The connection between combustion and life was proposed in 1668 by John Mayow of London, who noted that a candle and an animal in a confined space died simultaneously, and suggested that both consumed "spiritus nitroaereus" from the air (1). The similarity of animal life and combustion is most frequently ascribed to the English and Swedish chemists Priestley and Scheele, who independently, in 
1774, observed that bees or mice, respectively, and a flame made air unfit for each other. They noted that an organism and a flame confined in an enclosure both died at about the same time. During this era a widely accepted misconception was that a mysterious substance, phlogiston, was produced from flame or breath. As noted by McCollum (2), even Priestley and Scheele held to the concept, calling it dephlogisticated air or fire air. The idea persisted among scientists for many years (3) even after its refutation by Lavoisier. The thorough and precise work of Lavoisier, however, had "nailed it," correctly identifying oxygen consumption and carbon dioxide production by animals and a flame (1,2). He concluded that the heat produced was equal when expressed per unit of CO2 produced. It is uncertain who actually made the first measurements of heat energy release, as discussed by Blaxter (4). Both Crawford (5) and Lavoisier developed water-jacketed or ice-jacketed chamber calorimeters, respectively, the former concluding that heat production by combustion of organic substance in a flame or by animals was equivalent and a constant per unit of O2 consumed. The constancy of heat per O2 proved more generally accurate than Lavoisier's relation to CO2. The principles of O2-CO2 exchange increasing with 1) food consumption, 2) activity, and 3) cold ambiency were also noted by Lavoisier in a letter to a British scientist dated Nov 19, 1790 (1). The method of measurement is unknown because of his untimely death by guillotine on May 8, 1794 at the age of 51 y.
An important chapter in the development of energetics principles is recorded in the 220 page classic describing the >100 experiments of Regnault and Reiset (6). At the College of France, they developed a closed-circuit respiration chamber and conducted refined measurements with dogs, rabbits, frogs, reptiles, beetles, silkworms, earthworms, and marmots (hibernating and awake). Their work established the principle of respiratory quotient (R.Q.),3 CO2/O2, in characterizing variations in heat release per unit of gas exchange. R.Q. could vary within the same animal from 0.62 to 1.04 depending on diet type (meat to carbohydrate) and amount (fasting to ad libitum). Additional principles include relation of the R.Q. to variation of heat production (HP) per unit of oxygen consumed: HP increase following food consumption, termed "period of digestion," increases with thin or young animals; that O2 consumption and HP per unit of body weight is greater in small than in large animal species, and that hibernating or cold-blooded animals consumed much less O2 per body weight (BW). A startling finding was that even within bird species, O2/BW was 10 times greater in the smaller species.
The Surface Law and metabolic body size
The next principle, still debated today, is how best to describe or adjust for the changed metabolism with variation in body weight within and across species. Rubner (7) formulated, or perhaps popularized [see Brody (8)], the Surface Law: HP approximates 1000 kcal/m2 of body surface area, from measurements on several species ranging in size from 30-kg dogs to 0.018-kg mice. Animal measurements were made on fed and fasted animals, although primarily while fasted. Species anomalies included the rabbit with a low HP/m2, although it was noted that the rabbit fit well if the ears were removed. The Surface Law came to be challenged by several researchers, most notably Kleiber (9) and Brody (8), who proposed, from measurements on species ranging from mice to elephants, that HP across species was better related to body weight raised to the 3/4 power. A debate, which continues to today, developed between these 2 men and many other scientists regarding the appropriate exponent for BW. Some held that Brody's determined value of 0.734 or 0.73 should be used, whereas Kleiber argued for 0.75 for reasons of practical application and simplicity. Many other challenges arose over the years, particularly regarding the fit of this Kleiber-Brody Law to intraspecies growing or mature animals of varying body weights. Blaxter (4) summarized data from 54 species of 11 mammalian orders and found, except for insectivora, a similar exponential relation of 0.76 within or across order. For young to mature animals within species, however, a lower exponent of BW has been shown to provide a better fit to basal or maintenance metabolism. Brody noted that the exponent for the growing animal within species more nearly approximated 0.6 as also noted by Heusner (10). Yet another deviation from the Kleiber-Brody Law is evident for variations in metabolic rates of mature animals within species, yielding exponents ranging from 0.83 to 0.93 (4) (Table 1). St. Clair Taylor's weight maintenance experiments (11) with cattle also suggested an exponent near 1.0, and calorimetric measurements with mature equine suggested the exponent of 0.87 (12). The intraspecies growing and mature exponent considerations can be accommodated in a single expression. For example, bovine maintenance energy requirement (NEm) = 30 Wm0.23 W0.67, where Wm is weight at maturity and W is weight at any other growth phase, is equivalent to 77 W0.75 at a BW of 500 kg. At 200 kg BW, however, maintenance energy is estimated to be 7% greater by the first formula.
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Metabolic intensity
The next logical question asked was why was the metabolism of small homeothermic animals so much more intense. Many measurements were made of tissue O2 consumption by in vitro incubations with generally unsatisfying, contradictory results, e.g., variations in buffer used, substrate concentrations, etc. Most showed little difference in analogous tissue taken from different species, although some tissues were more metabolically active than others. Thyroid and catecholamine hormone effects were widely examined and certainly played thermogenic roles, but not enough to explain species variations. The concept of fat-free mass was used to successfully remove much of the variation in many cases but again proved unsatisfactory in equalizing MR per unit of BW across species with a wide range of BWs. The concept of intensive metabolism of visceral organs, e.g., the liver, was developed, particularly after methods had been perfected to allow O2 consumption measurements on individual organs or tissues of the body in vivo. Visceral organ mass variations and the O2 consumption of these tissues have been shown to account for a major portion of whole-animal metabolism and vary parallel to species O2/BW, plane of nutrition, and even during ontogeny. The MR of underweight, intermediate, and overweight human males and females has been accurately estimated by applying organ-specific MRs to organ weights of each individual as determined by magnetic resonance imaging (15).
The concept of proton leak across the inner mitochondrial membrane and the dissipation of energy as heat instead of its use to drive ATP synthesis have been widely examined, as has the Na+,K+ pump activity to maintain ion gradients. Both of these mechanisms constitute principal components of O2 consumption in all tissues of all species. Hulbert and Else (16) provide an extensive review of the mechanisms underlying MR or the "cost of living" variations among individuals, species, orders, and of tissues of these organisms. They review the experimental evidence that the increasing proportion of active organs per BW accounts for part of the high MR of small animals as the organ weights increase proportional to BW exponents of 0.85, suggesting that the balance of the changed MRs must arise from changing tissue specific MR. Also presented is extensive evidence for an intriguing theory that this increased small creature tissue specific MR is caused by, or at least related to, increased unsaturated fatty acid composition of membranes, particularly docosahexaenoic acid, a 22:6 PUFA. The shrew, for example, has a very high 22:6 and low monounsaturated fatty acid content. Proton leak rates across the inner mitochondrial membrane and Na pump activities among species correlate with the unsaturation of lipids in the membranes. Overall Hulbert and Else argue that membrane lipid saturation provides a mechanism fueling MRs to allow the evolution of endothermy.
Visceral organ mass variations also play an important role in another energetics principle well established by research with agricultural animal species, the concept of shifting MR within individuals in response to changes in plane of nutrition. The classic paper of Marston (17) showed that the postabsorptive MR of sheep, the fasting heat production, was elevated if the animal had received a higher plane of nutrition before the fast. These findings tie in to later research showing that weights of liver and gut expand and contract in proportion to the metabolic workload (18) and that maintenance energy requirements are not constant but vary with plane of nutrition. This principle has been incorporated into the ACC 1980 (19) Australian feeding standards. Although widely recognized, it has not been included in other world energy requirement schemes, at least not directly. The NRC beef system (20) can be said to incorporate the concept, but indirectly, by assuming a fixed maintenance level and reduced partial efficiencies above maintenance, a consequence of these levels having been determined by the slaughter balance procedure.
Development of feed, food composition, and energetic value
The connection of foods as the source of this fire, heat, energy and its connection with respiration and oxidation likely predate the brilliant confirmation by Lavoisier and his contemporaries. An example is the assertion of Ben Franklin in a 1757 treatise on evaporative cooling that "the human body is likely warmed by the combustion of food" (21). Early interest in chemical components was to define the medicinal value of foods exemplified by the work of Le Febure, a French apothecary, in 1660 [cited by McCollum (2)]. The first feed equivalence scheme, however, did not use chemical analysis. Albrecht Thaer, a physician and originator of the State Agricultural Institute at Moglin, Germany, noted in 1804 that well-cured hay for horses, cattle, and sheep kept these animals in good condition for a long time. He developed the Thaer hay equivalents relating all feeds to 10 lb of meadow hay (e.g., 1 hay unit = 9 lb clover hay, 45 lb wheat straw, 6 lb wheat grain, etc.).
Lusk (1) credits Magendie (22) as the first to separate foods into protein, fat, and carbohydrate components and the extensive studies of Liebig (23) to show that these were the components being burned in metabolism. Liebig, however, postulated that fat and carbohydrates were the source of oxidation, and protein was broken down but not oxidized by muscle work. He developed the theory of "plastic food," meaning the protein portion was the centrally important component, and equated all feeds to a "wheat flour equivalent" (e.g., 100 g wheat flour = 117 g oats, 613g potatoes, 67 g peas, etc.). This conceptual error coupled with his prominence as the authority of the day delayed progress in understanding of protein-energy interactions for perhaps 40 y. Extensive work on digestion and metabolism of fat, protein, and carbohydrates was published in 1852 by Bidder and Schmidt (24), who reported protein to be split into oxidized C and H and excreted N portions, in contrast to the "plastic food" dogma of Leibig. Their work was dismissed until several other animal and human experiments [e.g.,Voit (25)] refuted the Leibig concept of work involving muscle breakdown.
Rubner's (26) extensive calorimetric studies followed with concomitant determinations of the caloric content of excreta led to formulation of the Isodynamic Law: that food nutrients are interchangeable on an energy-equivalent basis, providing protein is adjusted for urea excretion in the urine (e.g., 100 g fat = 211 g protein, 232 g starch, 234 g sugar, etc). Henneberg and Stohman heavily influenced the evaluation of feeds and foods through their experiments with farm animals in the years following the establishment in 1860 of the Agricultural Experimental Station at Weende, Germany (2). In addition to refuting the Leibig protein model, they also began to explore the role(s) of plant cell wall fiber, incorporating the chemical analysis technique of Howard Harsford, a Harvard chemist who boiled grains in acid and then alkali successively to isolate the fiber. From these studies the Weende method of feedstuff analysis was developed. The technique separated all feeds into 5 components: water, fat, crude protein, crude fiber, and nitrogen-free extract by difference. This concept with relatively minor modifications, e.g., the Van Soest fiber analyses (27), is still widely used. Henneberg and Stohman also collected and analyzed feces and urine, exploring the digested and metabolized portions of nutritive ingredients of various feedstuffs. Much of the dietary cellulose and pentosans disappeared and were found in respiratory products, prompting the conclusion that fibrous components had nutritive value. Also noteworthy was that equivalence of digestible nutrients among feeds did not always result in equivalent animal responses, leading to respiration experiments and to evidence for unequal values of a unit of digestible energy depending on the source of dietary carbohydrate, a forerunner of the concept that heat increment varies with type of carbohydrate.
Early energetics research in the United States began when USDA scientists (28) built a Rubner-type calorimeter over a 5-y period and were successful in confirming that the Rubner heat production concepts established with dogs also applied to man. Shortly thereafter, the Rubner Isodynamic Law and specific dynamic effect of food were also shown to apply to cattle by Armsby [cited by Brody (8)], using similar direct/indirect respiration chamber calorimetry. An important result of Armsby's findings was that the specific dynamic effect was considerably greater in ruminants than in dog or man, which implied that this heat increment of feeding must be considered for feedstuff energy evaluation and led to the Net Energy (NE) concept.
The NE value of feedstuffs and parallel NE requirement of the animal have taken many forms and have generated a widely used principle for formulation of ruminant diets around the world. Early systems considered the NE value equal to the fraction of ME that was stored in product plus basal MR (29). Later research established the principle that the partial efficiency of ME use depended on the physiological function for which it was used by the animal. This led to the subscripting of the NE values and requirements, e.g., NEm, NEg, and NEl as values for utilization for maintenance, gain, and lactation (e.g., NRC, beef, dairy). The concept is also being applied to swine energy utilization and requirement schemes (30). Lower partial efficiencies of fiber as compared with starch-rich feeds are reported from these swine experiments analogous to those with cattle and sheep.
Animal experiments have revealed and continue to reveal factors controlling dietary energy requirements and use, including animal age, BW, sex, genotype, physiological stage, environment, activity, visceral organ mass, individuality, and the partial efficiency of dietary nutrient sources to meet these needs. Significant unexplained variations in energy use remain, particularly of biological causes of individual animal variations in MR and in the low partial efficiency of energy derived from microbially digested dietary cell wall substrates.
This article presents a rather incomplete sketch of major contributions of animal experiments to development of concepts of this "force of life." The reader is encouraged to explore further the works of these "wise men who have helped us learn new things" and, indeed, risk the likely missteps to become one of those "blessed ones who maketh due proof" to answer yet unexplained mysteries of energetics.
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FOOTNOTES |
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3 Abbreviations used: BW, body weight; HP, heat production; MR, metabolic rate; NE, net energy requirement; R.Q., respiratory quotient.
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LITERATURE CITED |
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TOPABSTRACTLITERATURE CITED |
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1. Lusk G. Science of nutrition. 4th ed. Philadelphia: Saunders; 1928.
2. McCollum EV. A history of nutrition. Boston: Houghton Mifflin; 1957.
3. Allchin D. James Hutton and phlogiston. Ann Sci. 1994;51:615–35.
4. Blaxter KL. Fasting metabolism and the energy requirements for maintenance. In: Festskrift til K. Breirem. Oslo: Mariendals Boktykkeri; 1972. p. 19–36.
5. Crawford A. Experiments and observations on animal heat. London: Printed for J. Johnson; 1788.
6. Regnault V, Reiset J. Recherché chimiques sur la respiration des animaux des diverse classes. Ann Chimie Physique. Ser. 3. 1849;26:299–519.
7. Rubner M. Die Gesetze des Energieverbrauchs bei der Ernahrung. Leipzig and Vienna: 1902.
8. Brody S. Bioenergetics and growth. New York: Hafner; 1945.
9. Kleiber M. The fire of life. New York: John Wiley; 1961.
10. Heusner AA. What does the power function reveal about structure and function in animals of different size? Annu Rev Physiol. 1987;49:121–33.[Medline]
11. Taylor StCS, Turner HG, Young GB. Genetic control of equilibrium maintenance efficiency in cattle. Anim Prod. 1981;33:179–94.
12. Pagan JD, Hintz HF. Equine energetics. II. Relationship between body weight and energy requirements in horses. J Anim Sci. 1986;63:815–20.
13. Dodds PS, Rothman DH, Weitz JS. Re-examination of the 3/4-law of metabolism. J Theor Biol. 2001;209:9–27.[Medline]
14. White CR, Seymour RS. Allometric scaling of mammalian metabolism. J Exp Biol. 2005;208:1611–19.
15. Bosy-Westphal A, Reinecke U, Schloreke T, Illner K, Kutzner D, Heller M, Muller MJ. Effect of organ and tissue masses on resting energy expenditure in underweight, normal weight and obese adults. Int J Obes Relat Metab Disord. 2004;28:72–9.[Medline]
16. Hulbert AJ, Else PL. Mechanisms underlying the cost of living in animals. Annu Rev Physiol. 2000;62:207–35.[Medline]
17. Marston HR. Energy transactions in the sheep. I. The basal heat production and heat increment. Aust J Sci Res. 1948;1:93–129.
18. Johnson DE, Johnson KA, Baldwin RL. Changes in liver and gastrointestinal tract energy demands in response to physiological workload in ruminants. J Nutr. 1990;120:649–55.
19. Feeding standards for Australian livestock: Ruminants. Victoria, Australia: CSIRO; 1980.
20. National Academy of Sciences. Nutrient requirements of beef cattle. Washington, DC: National Academy Press; 1996.
21. Franklin B. Letter to colleague in Charleston, Apr 14, 1757, cited in McCollum (2).
22. Magendie F. Precis elementaire de physiologie. 4th ed. Paris: Mequignon-Marvis; 1836, cited in Lusk (1).
23. Liebig J. Die organische chemie in ihrer anwendung auf physiologic und pathologie. Braunschweig; 1842, cited in Lusk (1).
24. Bidder F, Schmidt C. Die verdauungssafte und der stoffwechsel. Leipzig: Mitau; 1852, cited in Lusk (1).
25. Voit C. Physiologisch-chemische untersuchungen, Augsburg; 1857, cited in Lusk (1).
26. Rubner M. Sitzungsberichte der bayerischen Akademie der Wissenschraften; 1885. p. 454.
27. Goering HK, Van Soest PJ. Forage fiber analyses. Agriculture handbook 379, Washington, DC: U.S. Government Printing Office; 1970.
28. Atwater WO, Rosa EB. Description of a new respiration calorimeter and experiments on the conservation of energy in the human body. USDA, Office of Experiment Stations Bulletin No. 63. Washington (DC): US Government Print Office; 1899.
29. Morrison FB. Feeds and feeding. Ithaca, NY: Morison; 1957.
30. Noblet J, Fortune H, Shi XS, Dubois S. Prediction of net energy value of feeds for growing pigs. J Anim Sci. 1994;72:344–54.[Abstract]
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