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Impact of delivery temperature on uncoupling protein-1 and -2 abundance on brown adipose tissue in the newborn

Presented at the Neonatal Society 2004 Summer Meeting (programme).

Gnanalingham MG1, Clarke L2, Mostyn A1, Symonds ME1, Stephenson TJ1

1 Centre for Reproduction and Early Life, Institute of Clinical Research, University Hospital, Nottingham NG7 2UH, UK
2 Department of Agricultural Science, Imperial College London, Wye, Kent TN25 5AH, UK

Introduction: The uncoupling proteins (UCP) are members of the inner mitochondrial protein superfamily. The role of brown adipose tissue (BAT) UCP1 is clearly defined in non-shivering thermogenesis by promoting proton re-entry in and bypassing ATP synthase, while UCP2 has many postulated roles including thermogenesis, apoptosis and immunity. We have previously shown that delivery temperature is a major factor in brown adipose tissue function in the newborn (1). The extent to which delivery temperature affects the abundance of UCP1 and UCP2 mRNA in BAT has not yet been determined.

Methods: Eight triplet-bearing ewes were entered into the study. Four randomly selected ewes were given a 16μg dexamethasone (Dex) intramuscular injection at 138 days of gestation, followed by Caesarean section delivery at 140 days gestation (term ~ 147 days). The 4 untreated ewes (Controls) were also delivered by Caesarean section, but at 146 days. One lamb from each ewe was humanely euthanased (100 mg kg-1 pentobarbital sodium: Euthatal, i.v.) as a fetus to enable BAT dissection, while the remaining lambs were delivered either into a warm (WD, 30șC) or cool (CD, 15șC) ambient temperature, with tissue sampling at 6 hours of life. Total BAT RNA was extracted, reverse transcribed and UCP1 and 2 mRNA abundance measured by RT-PCR using oligonucleotide primers designed specifically to ovine UCP1 and 2. The mRNA results are given as means and standard errors (SEM) in arbitrary units, as a ratio of 18S rRNA and are expressed as a percentage of a reference sample. Statistical differences between groups were analysed by one-way ANOVA with post-hoc Bonferroni.

WD resulted in decreased UCP1 and UCP2 mRNA abundance in BAT from control groups. This effect was reduced with DEX treatment, resulting in WD groups having higher UCP1 and UCP2 mRNA abundance than their untreated controls (p<0.05). DEX WD resulted in reduced time to restore colonic temperature compared to DEX CD (WD 70 ± 7, CD 128 ± 22 minutes, p<0.05).

Conclusion: Delivery temperature is a major factor determining UCP1 and UCP2 mRNA abundance in neonatal BAT. The potentially reduced thermogenic capacity of BAT with WD may be blunted by antenatal DEX treatment, a response that is associated with improved thermoregulation.

1. Clarke L, Heasman L, Firth K and Symonds ME. Am J Physiol 1997; 272: R1931-39.

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