Register      Login
Animal Production Science Animal Production Science Society
Food, fibre and pharmaceuticals from animals
RESEARCH ARTICLE

The β3-adrenergic agonist (BRL35135A) acutely increases oxygen consumption and plasma intermediate metabolites in sheep

Samadi A C , M. Jois B , F. R. Dunshea A and B. J. Leury A D
+ Author Affiliations
- Author Affiliations

A Melbourne School of Land and Environment, The University of Melbourne, Parkville, Vic. 3010, Australia.

B School of Agriculture, La Trobe University, Bundoora, Vic. 3083, Australia.

C Present address: Agricultural Faculty, Animal Husbandry Department, Syiah Kuala University, Darussalam, Banda Aceh, Indonesia.

D Corresponding author. Email: brianjl@unimelb.edu.au

Animal Production Science 51(10) 881-889 https://doi.org/10.1071/AN10019
Submitted: 1 February 2010  Accepted: 28 July 2011   Published: 11 October 2011

Abstract

There is evidence that an atypical adrenoreceptor subtype is involved in mediating some of the physiological effects of catecholamines, particularly in some adipose tissue sites. Therefore, three experiments were conducted to determine the metabolic and energetic responses to oral administration of the purported β3-agonist BRL35135A in ruminant lambs. The post-prandial increase in O2 consumption (0.109 versus 0.139 L/min) and CO2 production (0.102 versus 0.127 L/min) at 30 min after feeding was greater (P < 0.05) in the lambs receiving 5 mg of the BRL35135A. Treatment × time interactions over the period between –50 and 220 min indicate significant increases in plasma non-esterified fatty acids (P < 0.001), glucose (P < 0.001) and lactate (P = 0.024) in lambs consuming a single oral dose of 5 mg BRL35135A. In a subsequent experiment there were similar interactions over the period between –120 and 1440 min for non-esterified fatty acids (P < 0.001), glucose (P < 0.001) and lactate (P < 0.001) in lambs consuming a lower oral dose of 1 mg BRL35135A. The effects of BRL35135A on plasma non-esterified fatty acids (P = 0.95), glucose (P = 0.84) and lactate (P = 0.68) were not modified by the β1- and β2-adrenergic antagonist alprenolol suggesting that the effects were mediated via β3-adrenergic receptor subtypes. In conclusion, these experiments indicate that BRL35135A is acutely active in sheep when given with feed, as indicated by increases in respiratory gas exchange and plasma metabolite concentrations.

Additional keywords: growth, metabolism.


References

Abe H, Minokoshi Y, Shimazu T (1993) Effect of a β3-adrenergic agonist, BRL35135A, on glucose uptake in rat skeletal muscle in vivo and in vitro. The Journal of Endocrinology 139, 479–486.
Effect of a β3-adrenergic agonist, BRL35135A, on glucose uptake in rat skeletal muscle in vivo and in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXitVynt7g%3D&md5=9a2180c623458fca3cbb135100d8b661CAS |

Arch JRS, Kaumann AJ (1993) Beta3 and atypical beta-adrenoreceptors. Medicinal Research Reviews 13, 663–729.
Beta3 and atypical beta-adrenoreceptors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXitlGqug%3D%3D&md5=ce29be2aadafd76089ef2dff7c458f78CAS |

Beermann DH (1993) β-adrenergic agonists and growth. In ‘The endocrinology of growth, development and metabolism in vertebrates’. (Eds MP Schriebman, CG Scanes, PK T Pang) pp. 345–366. (Academic Press: San Diego, CA)

Beermann DH, Dunshea FR (2005) ‘Animal agriculture’s future through biotechnology. Part 3. Metabolic modifiers for use in animal production.’ Issue paper 30. (Council for Agricultural Science and Technology: Iowa)

Beermann DH, Butler WR, Hogue DE, Fishell VK, Dalrymple RH, Ricks CA, Scanes CG (1987) Cimaterol-induced muscle hypertrophy and alter endocrine status in lambs. Journal of Animal Science 65, 1514–1524.

Bird JA, Mostyn A, Clarke L, Juniper DT, Budge H, Stephenson T, Symonds ME (2001) Effect of postnatal age and a β3-adrenergic agonist (Zeneca D7114) administration on uncoupling protein-1 abundance in the lamb. Experimental Physiology 86, 65–70.
Effect of postnatal age and a β3-adrenergic agonist (Zeneca D7114) administration on uncoupling protein-1 abundance in the lamb.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjvVeht74%3D&md5=b14fa5a74fbc07fceafe63eccdae710fCAS |

Byrem TM, Beermann DH, Robinson TF (1998) The beta-agonist cimaterol directly enhances chronic protein accretion in skeletal muscle. Journal of Animal Science 76, 988–998.

Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiological Reviews 84, 277–359.
Brown adipose tissue: function and physiological significance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXotl2qsQ%3D%3D&md5=0a376dc179c3b584a83edeac744aee35CAS |

Casteilla L, Muzzin P, Revelli JP, Ricquier D, Giacobino JP (1994) Expression of β1- and β3-adrenergic-receptor messages and adenylate cyclase β-adrenergic response in bovine perirenal adipose tissue during its transformation from brown into white fat. Biochemical Journal 297, 93–97.

Cawthorne MA, Sennitt MV, Arch JR, Smith SA (1992) BRL35135, a potent and selective atypical β-adrenoceptor agonist. The American Journal of Clinical Nutrition 55, 252S–257S.

Clarke L, Bird JA, Lomax MA, Symonds ME (1996) Effect of b3-adrenergic agonist (Zeneca D7114) on thermoregulation in near-term lambs delivered by cesarean section. Pediatric Research 40, 330–336.
Effect of b3-adrenergic agonist (Zeneca D7114) on thermoregulation in near-term lambs delivered by cesarean section.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK28visFensQ%3D%3D&md5=7431a675497a9706183281a2d890dda9CAS |

Dicker A, Aström G, Wåhlén K, Hoffstedt J, Näslund E, Wirén M, Rydén M, Arner P, van Harmelen V (2009) Primary differences in lipolysis between human omental and subcutaneous adipose tissue observed using in vitro differentiated adipocytes. Hormone and Metabolic Research. Hormon- und Stoffwechselforschung. Hormones et Metabolisme 41, 350–355.
Primary differences in lipolysis between human omental and subcutaneous adipose tissue observed using in vitro differentiated adipocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXnslGmsL4%3D&md5=36074fafd4e64346f69ed7cd59d52df1CAS |

Dulloo AG, Miller DS (1984) Thermogenetic drugs for the treatment of obesity: sympathetic stimulants in animal models. The British Journal of Nutrition 52, 179–196.
Thermogenetic drugs for the treatment of obesity: sympathetic stimulants in animal models.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXlsVCjsr4%3D&md5=b4e6f6480e050e2bfcedf5a68339a74aCAS |

Dunshea FR, King RH (1995) Response to homeostatic signals in ractopamine-treated pigs. The British Journal of Nutrition 73, 809–818.
Response to homeostatic signals in ractopamine-treated pigs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXmvVylsrw%3D&md5=4875d14d9624af626b09c7a6cb8bd8beCAS |

Dunshea FR, Bell AW, Trigg TE (1988) Relationships between plasma non-esterified fatty acid metabolism and body tissue mobilization during chronic undernutrition in goats. The British Journal of Nutrition 60, 633–644.
Relationships between plasma non-esterified fatty acid metabolism and body tissue mobilization during chronic undernutrition in goats.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1M7hvVWqtQ%3D%3D&md5=05699ca621e7e590439170800773a19dCAS |

Dunshea FR, Bell AW, Trigg TE (1989) Relationships between plasma non-esterified fatty acid metabolism and body fat mobilization in primiparous lactating goats. The British Journal of Nutrition 62, 51–61.
Relationships between plasma non-esterified fatty acid metabolism and body fat mobilization in primiparous lactating goats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXkvFCmtrk%3D&md5=08d32da0dcec5f289cd7b57ba35cde49CAS |

Dunshea FR, Bell AW, Trigg TE (1990) Non-esterified fatty acid and glycerol kinetics and re-esterification in early lactation goats. The British Journal of Nutrition 64, 133–145.
Non-esterified fatty acid and glycerol kinetics and re-esterification in early lactation goats.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXkvFGgtL4%3D&md5=9b90c04a3ebb8f34561ed4e0d3fa57cfCAS |

Dunshea FR, Leury BJ, King RH (1998) Lipolytic responses to catecholamines in ractopamine treated pigs. Australian Journal of Agricultural Research 49, 875–881.
Lipolytic responses to catecholamines in ractopamine treated pigs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXktFWrt7s%3D&md5=2c94cf1b424a37ae183d896d7e0b0ad9CAS |

Dunshea FR, D’Souza DN, Pethick DW, Harper GS, Warner RD (2005) Effects of dietary factors and other metabolic modifiers on quality and nutritional value of meat. Meat Science 71, 8–38.
Effects of dietary factors and other metabolic modifiers on quality and nutritional value of meat.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXmt1Wiu7g%3D&md5=2ba2d058915cc3c96cab189aa12c71a4CAS |

Eisemann JH, Huntington GB, Ferrell CL (1988) Effects of dietary clenbuterol on metabolism of the hindquarters in steers. Journal of Animal Science 66, 342–353.

Fain JN, Garcia-Sainz JA (1983) α-Adrenergic regulation of adipocyte metabolism. Journal of Lipid Research 24, 945–966.

Finn D, Lomax MA, Trayhurn P (1998) An immunohistochemical and in situ hybridization study of the postnatal development of uncoupling protein-1 and uncoupling protein-1 mRNA in lamb perirenal adipose tissue. Cell and Tissue Research 294, 461–466.
An immunohistochemical and in situ hybridization study of the postnatal development of uncoupling protein-1 and uncoupling protein-1 mRNA in lamb perirenal adipose tissue.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXmvFyitbg%3D&md5=95e9b58d824ede7daa3172ccd3aaccf8CAS |

Forrest RH, Hickford JGH, Hogan A, Frampton CM (2003) Polymorphism at the β3-adrenergic receptor locus: associations with birth weight, growth rate, carcass composition and cold survival. Animal Genetics 34, 19–25.
Polymorphism at the β3-adrenergic receptor locus: associations with birth weight, growth rate, carcass composition and cold survival.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXit1Kjsbg%3D&md5=b039f54e8fa09606e855eb7c3c6221acCAS |

Forrest RH, Hickford JGH, Frampton CM (2007) Polymorphism at the ovine β3-adrenergic receptor locus (ADRB3) and its association with lamb mortality. Journal of Animal Science 85, 2801–2806.
Polymorphism at the ovine β3-adrenergic receptor locus (ADRB3) and its association with lamb mortality.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtlWitbrN&md5=97490af8f485c588e7f7dff7ab702f6fCAS |

Gemmell RT, Bell AW, Alexander G (1972) Morphology of adipose cells in lambs at birth and during subsequent transition of brown to white adipose tissue in cold and in warm conditions. The American Journal of Anatomy 133, 143–163.
Morphology of adipose cells in lambs at birth and during subsequent transition of brown to white adipose tissue in cold and in warm conditions.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaE38%2FpsFCktA%3D%3D&md5=b4ec7ee81ee06bbae030f46d5c3caecdCAS |

Granneman JG, Burnazi M, Zhu Z, Schwamb LA (2003) White adipose tissue contributes to UCP1-independent thermogenesis. American Journal of Physiology. Endocrinology and Metabolism 285, E1230–E1236.

Grujic D, Susulic VS, Harper ME, Himms-Hagen J, Cunningham BA, Corkey BE, Lowell BB (1997) β3-adrenergic receptors on white and brown adipocytes mediate β3-selective agonist-induced effects on energy expenditure, insulin secretion and food intake. The Journal of Biological Chemistry 272, 17686–17693.
β3-adrenergic receptors on white and brown adipocytes mediate β3-selective agonist-induced effects on energy expenditure, insulin secretion and food intake.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXksFOksL8%3D&md5=4a50fcddf423f27d17048da44b603291CAS |

Hoffstedt J, Shimizu M, Sjöstedt S, Lönnqvist F (1995) Determination of beta 3-adrenoceptor mediated lipolysis in human fat cells. Obesity Research 3, 447–457.

Hyatt MA, Keisler DH, Budge H, Symonds ME (2010) Maternal parity and its effect on adipose tissue deposition and endocrine sensitivity in the postnatal sheep. Endocrinology 204, 173–179.
Maternal parity and its effect on adipose tissue deposition and endocrine sensitivity in the postnatal sheep.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXitV2jtL4%3D&md5=e233fff0fff8c39c350816424553ee53CAS |

Jéquier E, Munger R, Felber J-P (1992) Thermogenic effects of various β-adrenoceptor agonists in humans: their potential usefulness in the treatment of obesity. The American Journal of Clinical Nutrition 55, 249S–251S.

Kaicom S (1996) Manipulation of growth, carcass composition as well as milk yield and composition in sheep with the partitioning agent clenbuterol alone or with protected protein. PhD thesis, La Trobe University, Bundoora.

Lafontan M (1994) Differential recruitment and differential regulation by physiological amines of fat cell beta-1, beta-2 and beta-3 adrenergic receptors expressed in native fat cells and in transfected cell lines. Cellular Signalling 6, 363–392.
Differential recruitment and differential regulation by physiological amines of fat cell beta-1, beta-2 and beta-3 adrenergic receptors expressed in native fat cells and in transfected cell lines.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXmsVKgurs%3D&md5=667bce3c5d9d3af218b940d51cb07ae0CAS |

Lafontan M, Berlan M (1993) Fat cell adrenergic receptors and the control of white and brown fat cell function. Journal of Lipid Research 34, 1057–1064.

Lehninger AL, Nelson DL, Cox MM (1993) ‘Principles of biochemistry.’ 2nd edn. (Worth Publishers: New York)

Liu Y-L, Stock MJ (1995) Acute effects of the β3-adrenoceptor agonist, BRL35135, on tissue glucose utilisation. British Journal of Pharmacology 114, 888–894.

Lomax MA, Sadiq F, Karamanlidis G, Karamitri A, Trayhurn P, Hazlerigg DG (2007) Ontogenic loss of brown adipose tissue sensitivity to β-adrenergic stimulation in the ovine. Endocrinology 148, 461–468.

Lönnqvist F, Krief S, Strosberg AD, Nyberg S, Emorine LJ, Arner P (1993) Evidence for a functional beta 3-adrenoceptor in man. British Journal of Pharmacology 110, 929–936.

McNeel RL, Mersmann HJ (1999) Distribution and quantification of Beta1-, Beta2-, and Beta3-adrenergic receptor subtype transcripts in porcine tissues. Journal of Animal Science 77, 611–621.

Mersmann HJ (1989) Potential mechanisms for repartitioning of growth by β-adrenergic agonist. In ‘Animal growth regulation’. (Eds DR Champion, GJ Hausman, RJ Martin) pp. 337–57. (Plenum Press: New York)

Mersmann HJ (1998) Overview of the effect of β-adrenergic agonist receptor agonist on animal growth including mechanisms of action. Journal of Animal Science 76, 160–172.

Mersmann HJ (2002) Beta-adrenergic receptor modulation of adipocyte metabolism and growth. Journal of Animal Science 80, E24–E29.

National Research Council (1994) ‘Metabolic modifiers: effects on the nutrient requirements of food-producing animals.’ (National Academies Press: Washington, DC)

Newsholme EA, Leech AR (1983) ‘Biochemistry for the medical science.’ (John Wiley and Sons: New York)

Ostrowska E, Cross RF, Muralitharan M, Bauman DE, Dunshea FR (2002) Effects of dietary fat and conjugated linoleic acid on plasma metabolite concentrations and metabolic responses to homeostatic signals in pigs. The British Journal of Nutrition 88, 625–634.
Effects of dietary fat and conjugated linoleic acid on plasma metabolite concentrations and metabolic responses to homeostatic signals in pigs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXktFKitw%3D%3D&md5=37d5678e49c42eb1ec75e503617af2f5CAS |

Payne RW, Harding SA, Murray DA, Soutar DM, Baird DB, Welham SJ, Kane AF, Gilmour AR, Thompson R, Webster R, Tunnicliffe Wilson G (2008) ‘The guide to GenStat release 11, part 1: syntax and data management.’ (VSN International: Hemel Hempstead, UK)

Pietri-Rouxel F, Lenzen G, Kapoor A, Drumare M-F, Archimbault P, Strosberg AD, Manning BStJ (1995) Molecular cloning and pharmacological characterization of the bovine β3-adrenergic receptor. European Journal of Biochemistry 230, 350–358.
Molecular cloning and pharmacological characterization of the bovine β3-adrenergic receptor.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXlvFaltbw%3D&md5=eb86c8e8fc363d0b59d483b0ab460d03CAS |

Qvisth V, Hagström-Toft E, Enoksson S, Bolinder J (2008) Catecholamine regulation of local lactate production in vivo in skeletal muscle and adipose tissue: role of β-adrenoreceptor subtypes. The Journal of Clinical Endocrinology 93, 240–246.
Catecholamine regulation of local lactate production in vivo in skeletal muscle and adipose tissue: role of β-adrenoreceptor subtypes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXnsVyhtw%3D%3D&md5=c93e6c455574e6e686b2c0b932fac125CAS |

Reverte M, Rivas-Cabanero L (1996) Effects of the β3-adrenoceptor agonist BRL37344 on lipomobilisation and plasma glucose levels in conscious fasted rabbits. Canadian Journal of Physiology and Pharmacology 74, 251–256.
Effects of the β3-adrenoceptor agonist BRL37344 on lipomobilisation and plasma glucose levels in conscious fasted rabbits.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XjsVKhsrc%3D&md5=abb6b9ffa7dda0d8e9514726a7b28978CAS |

Reverte M, Garcia-Barrado MJ, Moratinos J (1991) Changes in plasma glucose and lactate evoked by alpha and beta-2 adrenoreceptor stimulation in conscious fasted rabbits. Fundamental & Clinical Pharmacology 5, 663–676.
Changes in plasma glucose and lactate evoked by alpha and beta-2 adrenoreceptor stimulation in conscious fasted rabbits.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK387kslShug%3D%3D&md5=7a1b0fb5731ef1c077793773fb1bc639CAS |

Rikhardsson G, Johnson KA, Johnson DE (1991) Effects of cimaterol on energetics and carcass characteristics of Suffolk ewe lambs. Journal of Animal Science 69, 396–404.

Smith SA, Sennitt MV, Cawthorne MA (1990) BRL 35135: an orally active antihyperglycaemic agent with weight reducing effects. In ‘New anti-diabetic drugs’. (Eds Bailey CJ, Flatt PR) pp. 177–189. (Smith-Gordon: London)

Spurlock ME, Cusumano JC, Ji SQ, Anderson DB, Smith CK, Hancock DL, Mills SE (1994) The effect of ractopamine on beta-adrenoceptor density and affinity in porcine adipose and skeletal muscle tissue. Journal of Animal Science 72, 75–80.

Weir JBDEV (1949) New methods for calculating metabolic rate with special reference to protein metabolism. The Journal of Physiology 109, 1–9.

Yoshida T (1992) The antidiabetic β3-adrenergic agonist BRL26830A works by release of endogenous insulin. The Journal of Clinical Nutrition 55, 237S–241S.

Zaagsma J, Nahorski S (1990) Is the adipocyte β-adrenoceptor a prototype for the recently cloned atypical β3-adrenoceptor? Trends in Pharmacological Sciences 11, 3–7.
Is the adipocyte β-adrenoceptor a prototype for the recently cloned atypical β3-adrenoceptor?Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK3c7ns12qsA%3D%3D&md5=4aae961b41e828ed4314b8f95e5f5000CAS |

Zhang J, Grieve DG, Coomber BL (1995) Effects of dietary protein and β-agonist on growth and fat deposition in prepubertal lambs. Canadian Journal of Animal Science 75, 219–224.
Effects of dietary protein and β-agonist on growth and fat deposition in prepubertal lambs.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXnvFynsbc%3D&md5=6eee92b95f84bf295c9d47cfdf741a17CAS |

Zimmerli UV, Blum JW (1990) Acute and longterm metabolic, endocrine, respiratory, cardiac and skeletal muscle activity changes in response to perorally administrated β-adrenoceptor agonist in calves. Journal of Animal Physiology and Animal Nutrition 63, 157–172.
Acute and longterm metabolic, endocrine, respiratory, cardiac and skeletal muscle activity changes in response to perorally administrated β-adrenoceptor agonist in calves.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXkt1amtr0%3D&md5=baeb280d23fe9aaafec03b8b81c126c9CAS |