Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-19T14:19:05.979Z Has data issue: false hasContentIssue false
  • English
  • Français

Development of a dynamic mathematical model for investigating mammary gland metabolism in lactating cows

Published online by Cambridge University Press:  03 September 2009

V. VOLPE ,
J. P. CANT ,
R. C. BOSTON ,
P. SUSMEL  and
P. MOATE
V. VOLPE*
Affiliation:
Department of Animal Science, University of Udine, 33010 Pagnacco (Ud), Italy
J. P. CANT
Affiliation:
Centre for Nutrition Modelling, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario N1G2W1, Canada
R. C. BOSTON
Affiliation:
Biostatistics Section, Department of Clinical Studies, University of Pennsylvania, Kennet Square, PA 19348, USA
P. SUSMEL
Affiliation:
Department of Animal Science, University of Udine, 33010 Pagnacco (Ud), Italy
P. MOATE
Affiliation:
Biostatistics Section, Department of Clinical Studies, University of Pennsylvania, Kennet Square, PA 19348, USA
*
*External contributor. To whom all correspondence should be addressed. Email: vvolpe@iol.it
Get access Rights & Permissions [Opens in a new window]

Summary

A dynamic mathematical model of a closed mammary system in lactating cows was developed to incorporate the setpoint concept of tissue activity, using equations where nutrient supply and absorption are locally regulated so as to maintain a given rate of milk protein yield. The model consists of 12 differential equations, 11 of which are concerned with intracellular biochemical compartments and one describes the volume of tissue actively perfused by blood (AP). The intracellular compartments are: amino acids (AAs), acetate, fatty acids (FAs), β-hydroxybutyrate, glucose-6-phosphate, fructose-6-phosphate, phospho-glyceraldehyde, pyruvate, mitochondrial acetyl-CoA, adenosine triphosphate (ATP) and adenosine diphosphate (ADP). The model simulates mechanisms which are aimed at reproducing and, thereby, explain variations in mammary plasma flow (MPF) observed experimentally. The AP changes according to variations in the metabolic status or in the metabolic requirements of the gland. Should the tissue energy charge (i.e. ATP/ADP ratio) exceed a baseline ratio, then AP decreases and consequently MPF declines. Conversely, when milk protein yield increases, AP increases and MPF rises. In the present model, AA uptake by the mammary gland is inhibited by intracellular AAs. It is also assumed that, when milk protein yield diminishes, the respiratory chain and ATP synthesis become uncoupled and consequently ATP yield is reduced. Model evaluation included behavioural analysis and sensitivity analysis. Behaviour analysis was conducted to test whether the model mechanisms reproduced the scenarios from which the model hypotheses were developed, and took into consideration: an increase in arterial glucose concentration (HIGLC), increases in arterial concentrations of non-esterified FAs, triacylglycerol and β-hydroxybutyrate (HIFAT), a 50% reduction of arterial histidine concentration (LOHIS), and a hyperinsulinaemic euglycaemic clamp (HIINS). Both HIGLC and HIFAT resulted in a decrease in MPF and in milk protein yield; moreover, the scenario HIGLC also produced a notable decrease in the extraction of glucose. The scenario LOHIS resulted in increased MPF and extraction of His from plasma. However these responses were not sufficiently large to prevent a severe reduction of milk protein yield which was accompanied by a reduction in the extraction of other essential AAs. The scenario HIINS resulted in an increase of MPF and of milk protein yield, in the extraction of His and of other essential AAs. Model sensitivity analysis focused on variation of both affinity and inhibition constants of some of the Michaelis–Menten equations. Improvements in model structure and directions for future research suggested by the modelling analysis are discussed.

Type
Modelling Animal Systems Paper
Information
The Journal of Agricultural Science , Volume 148 , Issue 1 , February 2010 , pp. 31 - 54
Copyright
Copyright © Cambridge University Press 2009

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Annison, E. F. (1983). Metabolite utilization by the ruminant mammary gland. In Biochemistry of Lactation (Ed. Mepham, T. B.), pp. 399–436. Amsterdam, The Netherlands: Elsevier Science Publishers B. V.Google Scholar
Backwell, F. R. C., Bequette, B. J., Wilson, D., Calder, A. G., Metcalf, J. A., Wray-Cahen, D., MacRae, J. C., Beever, D. E. & Lobley, G. E. (1994). Utilization of dipeptides by the caprine mammary gland for milk protein synthesis. American Journal of Physiology 267, R1–R6.Google ScholarPubMed
Baldwin, R. L. (1995). The modeling process II – solution algorithms, model evaluation and parameters estimation. In Modeling Ruminant Digestion and Metabolism (Ed. Baldwin, R. L.), pp. 75–117. London, UK: Chapman and Hall.Google Scholar
Baldwin, R. L. & Yang, Y. T. (1974). Enzymatic and metabolic changes in the development of lactation. In Lactation, Vol. 1 (Eds Larson, B. L. & Smith, V. R.), pp. 349–411. New York: Academic Press.Google Scholar
Bauman, D. E. & Davis, C. L. (1974). Biosynthesis of milk fat. In Lactation, Vol. 2 (Eds Larson, B. L. & Smith, V. R.), pp. 31–75. New York: Academic Press.Google Scholar
Baumrucker, C. R. (1985). Amino acid transport systems in bovine mammary tissue. Journal of Dairy Science 68, 2436–2451.CrossRefGoogle ScholarPubMed
Bequette, B. J. & Backwell, F. R. C. (1997). Amino acid supply and metabolism by the ruminant mammary gland. Proceedings of the Nutrition Society 56, 593–605.CrossRefGoogle ScholarPubMed
Bequette, B. J., Backwell, F. R. C., MacRae, J. C., Lobley, G. E., Crompton, L. A., Metcalf, J. A. & Sutton, J. D. (1996). Effect of intravenous amino acid infusion on leucine oxidation across the mammary gland of the lactating goat. Journal of Dairy Science 79, 2217–2224.CrossRefGoogle ScholarPubMed
Bequette, B. J., Backwell, F. R. C. & Crompton, L. A. (1998). Current concepts of amino acid and protein metabolism in the mammary gland of the lactating ruminant. Journal of Dairy Science 81, 2540–2559.CrossRefGoogle ScholarPubMed
Bequette, B. J., Hanigan, M. D., Calder, A. G., Reynolds, C. K., Lobley, G. E. & MacRae, J. C. (2000). Amino acid exchange by the mammary gland of lactating goats when histidine limits milk production. Journal of Dairy Science 83, 765–775.CrossRefGoogle ScholarPubMed
Bequette, B. J., Kyle, C. E., Crompton, L. A., Buchan, V. & Hanigan, M. D. (2001). Insulin regulates milk production and mammary gland and hind-leg amino acid fluxes and blood flow in lactating goats. Journal of Dairy Science 84, 241–255.CrossRefGoogle ScholarPubMed
Bickerstaffe, R., Annison, E. F. & Linzell, J. L. (1974). The metabolism of glucose, acetate, lipids and amino acids in lactating dairy cows. Journal of Agricultural Science, Cambridge 82, 71–85.CrossRefGoogle Scholar
Cant, J. P. & McBride, B. W. (1995). Mathematical analysis of the relationship between blood flow and uptake of nutrients in the mammary glands of a lactating cow. Journal of Dairy Research 62, 405–422.CrossRefGoogle ScholarPubMed
Cant, J. P., De Peters, E. J. & Baldwin, R. L. (1993 a). Mammary amino acid utilization in dairy cows fed fat and its relationship to milk protein depression. Journal of Dairy Science 76, 762–774.CrossRefGoogle ScholarPubMed
Cant, J. P., DePeters, E. J. & Baldwin, R. L. (1993 b). Mammary uptake of energy metabolites in dairy cows fed fat and its relationship to milk protein depression. Journal of Dairy Science 76, 2254–2265.CrossRefGoogle Scholar
Cant, J. P., Qiao, F. & Toerien, C. A. (1999). Regulation of mammary metabolism. In Proceedings of the VIIIth International Symposium on Protein Metabolism and Nutrition (Eds Lobley, G. E., White, A. & MacRae, J. C.), pp. 203–219. Wageningen, The Netherlands: Wageningen Press.Google Scholar
Cant, J. P., Trout, D. R., Qiao, F. & McBride, B. W. (2001). Milk composition responses to unilateral arterial infusion of complete and histidine-lacking amino acid mixtures to the mammary glands of cows. Journal of Dairy Science 84, 1192–1200.CrossRefGoogle Scholar
Cant, J. P., Trout, D. R., Qiao, F. & Purdie, N. G. (2002). Milk synthetic response of the bovine mammary gland to an increase in the local concentration of arterial glucose. Journal of Dairy Science 85, 494–503.CrossRefGoogle Scholar
Cant, J. P., Berthiaume, R., Lapierre, H., Luimes, P. H., McBride, B. W. & Pacheco, D. (2003). Responses of the bovine mammary glands to absorptive supply of single amino acids. Canadian Journal of Animal Science 83, 341–355.CrossRefGoogle Scholar
Capuco, A. V., Wood, D. L., Baldwin, R., McLeod, K. & Paape, M. J. (2001). Mammary cell number, proliferation, and apoptosis during a bovine lactation: relation to milk production and effect of bST. Journal of Dairy Science 84, 2177–2187.CrossRefGoogle ScholarPubMed
Cherepanov, G. G., Danfær, A. & Cant, J. P. (2000). Simulation analysis of substrate utilization in the mammary gland of lactating cows. Journal of Dairy Research 67, 171–188.CrossRefGoogle ScholarPubMed
Christensen, H. N. (1990). Role of amino acid transport and counter transport in nutrition and metabolism. Physiological Reviews 70, 43–77.CrossRefGoogle Scholar
Dado, R. G., Mertens, D. R. & Shook, G. E. (1993). Metabolizable energy and absorbed protein requirements for milk component production. Journal of Dairy Science 76, 1575–1588.CrossRefGoogle ScholarPubMed
Dalgleish, D. G. (1993). Bovine milk protein properties and the manufacturing quality of milk. Livestock Production Science 35, 75–93.CrossRefGoogle Scholar
Dils, R. R. (1983). Milk fat synthesis. In Biochemistry of Lactation (Ed. Mepham, T. B.), pp. 141–157. Amsterdam, The Netherlands: Elsevier Science Publishers, B. V.Google Scholar
Ebner, K. E. & Schanbacher, F. L. (1974). Biochemistry of lactose and related carbohydrates. In Lactation, Vol. 2 (Eds Larson, B. L. & Smith, V. R.), pp. 77–113. New York: Academic Press.Google Scholar
Forsberg, N. E., Baldwin, R. L. & Smith, N. E. (1984). Roles of acetate and its interactions with glucose and lactate in cow mammary tissue. Journal of Dairy Science 67, 2247–2254.CrossRefGoogle ScholarPubMed
Forsberg, N. E., Baldwin, R. L. & Smith, N. E. (1985). Roles of glucose and its interactions with acetate in maintenance and biosynthesis in bovine mammary tissue. Journal of Dairy Science 68, 2544–2549.CrossRefGoogle ScholarPubMed
Gibb, M. J., Ivings, W. E., Dhanoa, M. S. & Sutton, J. D. (1992). Changes in body components of autumn-calving Holstein–Friesian cows over the first 29 weeks of lactation. Animal Production 55, 339–360.Google Scholar
Griinari, J. M., McGuire, M. A., Dwyer, D. A., Bauman, D. E. & Palmquist, D. L. (1997 a). Role of insulin in the regulation of milk fat synthesis in dairy cows. Journal of Dairy Science 80, 1076–1084.CrossRefGoogle ScholarPubMed
Griinari, J. M., McGuire, M. A., Dwyer, D. A., Bauman, D. E., Barbano, D. M. & House, W. A. (1997 b). The role of insulin in the regulation of milk protein synthesis in dairy cows. Journal of Dairy Science 80, 2361–2371.CrossRefGoogle ScholarPubMed
Guinard, J. & Rulquin, H. (1994). Effects of graded amounts of duodenal infusions of lysine on the mammary uptake of major milk precursors in dairy cows. Journal of Dairy Science 77, 3565–3576.CrossRefGoogle ScholarPubMed
Hanigan, M. D. & Baldwin, R. L. (1994). A mechanistic model of mammary gland metabolism in the lactating cow. Agricultural Systems 45, 369–419.CrossRefGoogle Scholar
Hanigan, M. D., Crompton, L. A., Metcalf, J. A. & France, J. (2001). Modelling mammary metabolism in the dairy cow to predict milk constituent yield, with emphasis on amino acid metabolism and milk protein production: model construction. Journal of Theoretical Biology 213, 223–239.CrossRefGoogle ScholarPubMed
Hurtaud, C., Gelly, C., Chen, Z., Levi-Meyrueis, C. & Bouillaud, F. (2007). Glutamine stimulates translation of uncoupling protein 2mRNA. Cellular and Molecular Life Sciences 64, 1853–1860.CrossRefGoogle ScholarPubMed
Jorgensen, G. N. & Larson, B. L. (1968). Conversion of phenylalanine to tyrosine in the bovine mammary secretory cell. Biochimica et Biophysica Acta 165, 121–126.CrossRefGoogle ScholarPubMed
Kemp, R. G. & Markus, F. (1990). Effects of fructose-2,6-biphosphate on 6-phosphofructo-1-kinase and fructose-1,6-biphosphatease. In Fructose-2,6-biphosphate (Ed. Pilkis, S. J.), pp. 17–37. Boca Raton, FL: CRC Press.Google Scholar
Korhonen, M., Vanhatalo, A. & Huhtanen, P. (2002). Evaluation of isoleucine, leucine, and valine as a second-limiting amino acid for milk production in dairy cows fed grass silage diet. Journal of Dairy Science 85, 1533–1545.CrossRefGoogle ScholarPubMed
Laughlin, M. H. & Korzick, D. H. (2001). Vascular smooth muscle: integrator of vasoactive signals during exercise hyperemia. Medicine and Science in Sports and Exercise 33, 81–91.CrossRefGoogle ScholarPubMed
Ledesma, A., De Lacoba, M. G. & Rial, E. (2002). The mitochondrial uncoupling proteins. Genome Biology 3, reviews3015.1–3015.9.CrossRefGoogle ScholarPubMed
Mackle, T. R., Dwyer, D. A., Ingvartsen, K. L., Chouinard, P. Y., Lynch, J. M., Barbano, D. M. & Bauman, D. E. (1999). Effects of insulin and amino acids on milk protein concentration and yield from dairy cows. Journal of Dairy Science 82, 1512–1524.CrossRefGoogle ScholarPubMed
Mackle, T. R., Dwyer, D. A., Ingvartsen, K. L., Chouinard, P. Y., Ross, D. A. & Bauman, D. E. (2000). Effects of insulin and postruminal supply of protein on use of amino acids by the mammary gland for milk protein synthesis. Journal of Dairy Science 83, 93–105.CrossRefGoogle ScholarPubMed
Mepham, T. B. (1982). Amino acid utilization by the lactating mammary gland. Journal of Dairy Science 65, 287–298.CrossRefGoogle ScholarPubMed
Metcalf, J. A., Wray-Cahen, D., Chettle, E. E., Sutton, J. D., Beever, D. E., Crompton, L. A., Macrae, J. C., Bequette, B. J. & Backwell, F. R. C. (1996). The effect of dietary crude protein as protected soybean meal on mammary metabolism in the lactating dairy cow. Journal of Dairy Science 79, 603–611.CrossRefGoogle ScholarPubMed
Miller, P. S., Reis, B. L., Calvert, C. C., De Peters, E. J. & Baldwin, R. L. (1991). Patterns of nutrient uptake by the mammary glands of lactating dairy cows. Journal of Dairy Science 74, 3791–3799.CrossRefGoogle ScholarPubMed
Petzke, K. J., Friedrich, M., Metges, C. C. & Klaus, S. (2005). Long-term dietary high protein intake up-regulates tissue specific gene expression of uncoupling proteins 1 and 2 in rats. European Journal of Nutrition 44, 414–421.CrossRefGoogle ScholarPubMed
Prosser, C. G., Davis, S. R., Farr, V. C. & Lacasse, P. (1996). Regulation of blood flow in the mammary microvasculature. Journal of Dairy Science 79, 1184–1197.CrossRefGoogle ScholarPubMed
Purdie, N. G., Trout, D. R., Poppi, D. P. & Cant, J. P. (2008). Milk synthetic response of the bovine mammary gland to an increase in the local concentration of amino acids and acetate. Journal of Dairy Science 91, 218–228.CrossRefGoogle Scholar
Renkin, E. M. (1984). Control of microcirculation and blood-tissue exchange. In Handbook of Physiology, Section 2. The Cardiovascular System (Eds Renkin, E. M. & Michel, C. C.), pp. 627–687. Bethesda, MD: American Physiological Society.Google Scholar
Ricquier, D. & Bouillaud, F. (2000). Mitochondrial uncoupling proteins: from mitochondria to the regulation of energy balance. Journal of Physiology 529, 3–10.CrossRefGoogle Scholar
Shennan, D. B., Millar, I. D. & Calvert, D. T. (1997). Mammary-tissue amino acid transport systems. Proceedings of the Nutrition Society 56, 177–191.CrossRefGoogle ScholarPubMed
Stefanovski, D., Moate, P. J. & Boston, R. C. (2003). WinSAAM: A windows-based compartmental modeling system. Metabolism 52, 1153–1166.CrossRefGoogle ScholarPubMed
Walstra, J. & Jenness, R. (1984). Dairy Chemistry and Physics. New York: John Wiley and Sons.Google Scholar
Wastney, M. E., Patterson, B. H., Linares, O. A., Greif, P. C. & Boston, R. C. (1999). Investigating Biological Systems using Modeling: Strategies and Software. San Diego, CA: Academic Press.Google Scholar
Weekes, T. L., Luimes, P. H. & Cant, J. P. (2006). Responses to amino acid imbalances and deficiencies in lactating dairy cows. Journal of Dairy Science 89, 2177–2187.CrossRefGoogle ScholarPubMed
Wright, T. C., Cant, J. P. & McBride, B. W. (2002). Inhibition of fatty acid synthesis in bovine mammary homogenate by palmitic acid is not a detergent effect. Journal of Dairy Science 85, 642–647.CrossRefGoogle Scholar
Wright, T. C., Cant, J. P. & McBride, B. W. (2008). Use of metabolic control analysis in lactation biology. Journal of Agricultural Science, Cambridge 146, 267–273.CrossRefGoogle Scholar