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Metabolic Modifiers: Advances in Economic Production of Safe Food

ROBERT J. COLLIER

University of Arizona

Metabolic modifiers are classified as compounds that alter metabolism in order to achieve an improvement in efficiency of a productive process. This may include improvements in growth rate, milk yield, body composition, or in nutrient utilization. Metabolic modifiers can have more than one function (pleiotropy), and different metabolic modifiers may cause the same biologic effect (redundancy) (Klasing et al., 1991). A challenge for animal producers is how to assess effects of metabolic modifiers on nutrient requirements of livestock.

A review of metabolic modifiers by Boyd and Bauman (1991) demonstrated that some compounds, like antibiotics, affect both growth and digestion because they influence microbial populations and digestive tract efficiency. Other compounds, such as anabolic steroids, alpha-adrenergic agonists, and somatotropins, which affect metabolism and utilization of absorbed nutrients and raise other considerations, such as effects on nutrient requirements.

These considerations are addressed in the review by Boyd and Bauman (1991), which introduced a flow chart to evaluate the impact of metabolic modifiers on nutrient requirements. The flow chart provides a key to safe, effective, and profitable use of metabolic modifiers on the farm. According to phase I (Figure 4–1), if the digestive process is altered by the metabolic modifier, then specific nutrient dietary concentrations should be altered in direct proportion to changes in digestibility. If other dimensions of animals performance are affected, then the phase II (Figure 4–2), which determines post



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Scientific Advances in Animal Nutrition: Promise for the New Century, Proceedings of a Symposium 4 Metabolic Modifiers: Advances in Economic Production of Safe Food ROBERT J. COLLIER University of Arizona Metabolic modifiers are classified as compounds that alter metabolism in order to achieve an improvement in efficiency of a productive process. This may include improvements in growth rate, milk yield, body composition, or in nutrient utilization. Metabolic modifiers can have more than one function (pleiotropy), and different metabolic modifiers may cause the same biologic effect (redundancy) (Klasing et al., 1991). A challenge for animal producers is how to assess effects of metabolic modifiers on nutrient requirements of livestock. A review of metabolic modifiers by Boyd and Bauman (1991) demonstrated that some compounds, like antibiotics, affect both growth and digestion because they influence microbial populations and digestive tract efficiency. Other compounds, such as anabolic steroids, alpha-adrenergic agonists, and somatotropins, which affect metabolism and utilization of absorbed nutrients and raise other considerations, such as effects on nutrient requirements. These considerations are addressed in the review by Boyd and Bauman (1991), which introduced a flow chart to evaluate the impact of metabolic modifiers on nutrient requirements. The flow chart provides a key to safe, effective, and profitable use of metabolic modifiers on the farm. According to phase I (Figure 4–1), if the digestive process is altered by the metabolic modifier, then specific nutrient dietary concentrations should be altered in direct proportion to changes in digestibility. If other dimensions of animals performance are affected, then the phase II (Figure 4–2), which determines post

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Scientific Advances in Animal Nutrition: Promise for the New Century, Proceedings of a Symposium absorptive nutrient changes, should be followed. According to phase II, if a metabolic modifier alters composition and rate of gain, then the nutrient-calorie ratio and the daily intake of specific nutrients should be altered as appropriate. SOMATOTROPIN INCREASES MILK PRODUCTION This flow chart (Figure 4-1) can be effectively applied to somatotropin, a 190- or 191-amino acid homeorhetic molecule that coordinates metabolism and controls nutrient flow to support a specific physiologic state (McGuire and Bauman, 1997). Somatotropin increases efficiency of growing and lactating animals through multiple sites of action. In a lactating animal, somatotropin affects a wide variety of tissues to coordinate metabolism to support increases in milk production. In a growing animal, somatotropin supports nutrient flow to lean muscle accretion and bone mass. Because lean mass is increased in growing animals, the nutrient requirements are altered. This is not the case in the lactating dairy cow where additional nutrients required are determined by the size of the increase in milk yield. There is no net change in lean body mass. FIGURE 4–1. Phase I: Digestive Process (Boyd and Bauman, 1991).

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Scientific Advances in Animal Nutrition: Promise for the New Century, Proceedings of a Symposium FIGURE 4–2. Phase II: Post-Absorptive Nutrient Use (Boyd and Bauman, 1991). High-producing lactating dairy cows have higher concentrations of blood somatotropins than do lower producing dairy cows, but these levels are elevated only during lactation. This is because during lactation, the secretion rate of somatotropin from the pituitary gland is higher in high producing dairy cows (Hart et al., 1980). Injecting somatotropin in lactating dairy cows mimics rate of genetic progression. Somatotropin does not affect basal metabolic requirements

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Scientific Advances in Animal Nutrition: Promise for the New Century, Proceedings of a Symposium or the efficiency of utilization of energy for milk production in the lactating dairy cow; so, nutrient requirements can be calculated from the increase of milk yield. Nutrients in excess of National Research Council (NRC) requirements should not produce any further benefits and research supports this claim. Bauman and coworkers (1999) examined the impact of somatotropin use in dairy herds by matching the somatotropin customer database from Monsanto Company with the Dairy Herd Improvement Association data for the northeast region for the period of 1990 to 1998. Herds that never adopted somatotropin were compared with herds that had maintained at 50 percent or more in herd use rate of somatotropin. Herd size and milk production were relatively constant between the two groups. Herds that adopted bovine somatotropin (bST) maintained an average increase of milk production of six pounds per cow per day across the entire time period. Since only 70 percent of any of the cows could be treated at any one time (because cows are treated at 60 days into lactation) the actual increase in treated cows was actually about 10 pounds per day. This study supported the clinical trial data. But more importantly, it demonstrated that current nutritional recommendations are adequate because dairy producers consistently maintained a milk yield response from one year to the next. Other components, such as protein were not affected -- they increased in proportion to milk yield increases. Average days in milk were similar for control and bST herds, indicating that somatotropin did not contribute to health deterioration. Decreased days in milk in 1994–1995 were attributed to feed costs and not bST. SOMATOTROPIN ENHANCES GROWTH When somatotropin is administered to enhance growth, maintenance requirements are increased because mean muscle mass is increased. Ideal protein intake in a set of growing boars administered porcine somatotropin (pST) was increased as lean muscle accretion increased (Etherton and Bauman, 1998). Protein requirements also increase in ruminants but are more difficult to measure because some of the protein bypasses the rumen; some is degraded into amino acids, and some is used as microbial protein composition (Etherton and Bauman, 1998). One of several models developed to estimate ruminant protein requirements is The Cornell Net Carbohydrate and Protein System. Data for this model were developed by using actual net protein requirements as a baseline and then infusing casein into the abomasum to increase protein availability until the observed and predicted increase in actual protein were the same. While progress is being made to understand the nutrient requirements of growing animals given somatotropin, variable amino acid availability estimates have caused the response to somatotropin also be variable.

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Scientific Advances in Animal Nutrition: Promise for the New Century, Proceedings of a Symposium METABOLIC MODIFIERS ON THE HORIZON Bovine Placental Lactogen Another metabolic modifier of recent interest is bovine placental lactogen, a molecule produced during pregnancy (Collier et al., 1995). Bovine placental lactogen promotes mammary development during pregnancy. Placental lactogen binds to both the growth hormone and prolactin receptors and affects local IGFI availability at the mammary gland. This molecule is also galactopoetic in lactating cows and promotes growth in growing animals. Growth studies utilizing both placental lactogen and growth hormone have demonstrated a synergistic effect on growth. This appeared to be mediated in part by increases in feed intake induced by placental lactogen, possibly through the prolactin receptor, which are not apparent with somatotropin alone. Milk yield responses to placental lactogen are not as pronounced as with somatotropin, but feed intake is increased through its prolactin-like action. Because of the increase in feed intake, net energy balance is increased in lactating dairy cows treated with bovine placental lactogen. A bST-treated cow increases milk yield immediately, but feed intake does not adjust for at least 8 weeks. However, placental lactogen-treated animals immediately increase their intake. Thus, placental lactogen has potential for use early in lactation when energy balance is negative or possibly in growing animals to increase feed intake. Conjugated Linoleic Acid Another new metabolic modifier, conjugated linoleic acid (CLA), has real opportunity for domestic animals. The term CLA refers to a mixture of positional and geometric conjugated dienes of linoleic acid. Feeding a mixture of CLA isomers decreases fat deposition and therefore increases per cent lean mass in growing pigs (Ostrowska et al., 1999). The reduction in fat deposition reduces energy needs to achieve market weight and thus has value to producers. Interest in using CLA to improve food composition has grown since several additional properties related to human health have been shown such as its anticarcinogenic effects (Ip et al., 1994). Although Ostrowska et al. (1999) demonstrated dramatic effects of CLA on body composition, they also pointed out that improvement in feed to gain ratio was not as large as expected and may indicate an alteration in metabolic rate. Thus, much additional work is needed to estimate impact of CLA on nutrient requirements. CONCLUSIONS Metabolic modifiers have long been recognized as effective tools in improving efficiency of domestic animal production. However, some of these tools such as bST, antibiotics, and steroids have come under increasing pressure

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Scientific Advances in Animal Nutrition: Promise for the New Century, Proceedings of a Symposium due to consumer health concerns. Research to identify new and improved methods of altering nutrient requirements and efficiency of production is justified and essential to continued improvements in domestic livestock production. Compounds such as CLA offer added value to livestock production by improving the quality and health benefits of consumer products. REFERENCES Bauman, D. E., R. W. Everett, W. H. Weiland, and R. J. Collier. 1999. Production responses to bovine somatotropin in northeast dairy herds. J. Dairy Sci. 82:2564-2573. Boyd, R.D., D.E. Bauman, D. G. Fox, and C.G. Scanes.1991. Impact of metabolism modifiers on protein accretion and on protein and energy requirements of domestic animals J. Anim. Sci. 69(Suppl.2):56-75. Collier, R.J., J.C. Byatt, M.F. McGrath, and P.J. Eppard.1995.Role of bovine placental lactogen in intercellular signaling during mammary growth and lactation. In: Intercellular Signalling in the Mammary Gland. Ed by C.J. Wilde et al., Plenum Press, New York, pp.13-24. Collier, R.J., and J.C. Byatt. 1998. Somatotropin in Domestic Animals. In: Agricultural Biotechnology. Ed. A. Altman, Marcel Dekker, Inc, New York. PP. 483-497. Etherton, T.D., and D. E. Bauman. 1998. Biology of Somatotropin in Growth and Lactation of Domestic Animals. Physiol. Rev. 78:745-759. Hart, I.C., J.A. Bines, and S. V. Morant. 1980. The secretion and metabolic clearance rates of growth hormone, insulin and prolactin in high- and low-yielding cattle at four stages of lactation. Life Sci. 27:1840-1847. Ip, C. M. Singh, H.J. Thompson, and J.A. Scimeca. 1994. Conjugated linoleic acid suppresses mammary carcinogenesis and proliferative activity of the mammary gland in the rat . Cancer Res. 54:1212-1215. Klasing, K.C., W.C. Wagner, and K.W. Kelley. 1991. Impact of metabolic modifiers on target animal health and environmental safety with emphasis on somatotropin. J. Anim. Sci 69(Suppl. 2):88-99. McGuire, M.A., and D. E. Bauman. 1997. Regulation of nutrient use by bovine somatotropin: the key to animal performance and well-being. In: IXth International Conference on Production diseases in Farm Animals 1995. ed. By H. Martens.-Stuttgart:Enke Ostrowska, E., M. Muralithran, R.F. Cross, D. E Bauman, and F. R. Dunshea 1999. Dietary conjugated linoleic acids increase lean tissue and decrease fat deposition in growing pigs. J. Nutr. 129:2037-2042.