The metabolic responses that occur during the transition from fetal to neonatal life represent a change from a thermo- regulatory quiescent state, in which inhibitory factors dominate (Gunn & Gluckman, 1995), to one of near-maximal rates of heat production that are rarely matched again during postnatal or adult life. Newborn lambs must therefore possess sufficient energy reserves in the form of lipid within adipose tissue depots and hepatic glycogen, since a large proportion of energy requirements for heat production immediately after birth comes from the mobilisation of these stores (Alexander, 1961; Mellor & Cockburn, 1986). At the same time, lambs must be able to rapidly activate non-shivering thermogenesis in brown adipose tissue (BAT) (Clarke et al. 1997c) because shivering is an inefficient method of increasing heat production due to disruption of the boundary layer of air around the lamb, which can contribute to heat loss (Alexander, 1979). An inability to produce sufficient heat by non-shivering thermogenesis in conjunction with exposure to a cold extrauterine environment and starvation is a major cause of the 1–4 million lamb deaths occurring annually in the UK. The generation of heat via non-shivering thermogenesis in BAT is due to the presence of a unique uncoupling protein (UCP1) which uncouples oxidative phosphorylation from adenosine triphosphate synthesis and releases energy as heat (Cannon & Nedergaard, 1985). Non-shivering thermogenesis in BAT does not normally occur in utero, as fetal body temperature follows that of the mother (Gunn & Gluckman, 1983). Messenger RNA for UCP1 and its thermogenic activity remain low during fetal life but rise rapidly after birth (Casteilla et al. 1989; Clarke et al. 1997a) as the newborn establishes independent thermoregulatory mechanisms. In lambs, the thermogenic activity doubles within 2 h of birth (Clarke et al. 1997a), a response which is mediated in part by the rapid increase in activity of the sympathetic nervous Effect of postnatal age and a b 3 -adrenergic agonist (Zeneca D7114) administration on uncoupling protein-1 abundance in the lamb J. A. Bird*, A. Mostyn, L. Clarke†, D. T. Juniper‡, H. Budge, T. Stephenson and M. E. Symonds § Academic Division of Child Health, School of Human Development, University Hospital, Queen’s Medical Centre, Nottingham NG7 2UH, *The Nightingale Institute, Division of Nursing and Midwifery, School of Life, Basic and Medical Health Sciences, Kings College, London SE1 9RT, †Department of Agriculture and Horticulture, Wye College, University of London, Wye, Ashford TN25 5AH and ‡Department of Agriculture, University of Reading, Reading RG 6 6AJ, UK (Manuscript received 7 April 2000; accepted 1 December 2000) We examined the effect of time after birth and b 3 -adrenergic agonist (Zeneca D7114) administration on uncoupling protein-1 (UCP1) abundance and thermoregulation in the lamb. Forty twin lambs, all born normally at term, were maintained at a cold ambient temperature of between 3 and 8 °C. At 0.5, 1.75, 5.25, 11.25 and 23.25 h after birth eight sets of twins were fed 20 ml of formula milk ± 10 mg kg _1 of b 3 -adrenergic agonist, and 45 min after feeding brown adipose tissue (BAT) was sampled. Colonic temperature was measured and BAT analysed for UCP1 abundance, GDP- binding to mitochondrial protein (i.e. thermogenic activity) and catecholamine content. Colonic temperature declined between 1.25 and 6 h from 40.2 °C to 39.2 °C and then increased to 39.8 °C at 12 h, but increased after feeding at all ages. UCP1 abundance increased from 1.25 h after birth, to peak at 2 h after birth in controls, compared with 6 h after birth in b 3 -adrenergic agonist-treated lambs. The level of GDP-binding to mitochondrial protein did not change significantly with age but was increased by b 3 -adrenergic agonist treatment. The noradrenaline (norepinephrine) content of BAT increased between 1.25 and 12 h after birth, irrespective of b 3 -adrenergic agonist administration. The total weight of perirenal BAT plus its lipid, protein and mitochondrial protein content declined over the first 6 h of life. UCP1 development continues over the first 24 h of neonatal life, and can be manipulated by b 3 -adrenergic agonist administration. This may represent one method of improving thermoregulation in newborn lambs. Experimental Physiology (2001) 86.1, 65–70. 2046 Publication of The Physiological Society § Corresponding author: Michael.Symonds@nottingham.ac.uk ) by guest on July 13, 2011 ep.physoc.org Downloaded from Exp Physiol (