Submitted on May 18, 2005
Accepted on August 1, 2005
Differential effects of leptin administration on the abundance of uncoupling protein-2 and glucocorticoid action during neonatal development
M G Gnanalingham1, A Mostyn1, R Webb1, D H Keisler2, N Raver3, M C Alves-Guerra4, C Pecqueur4, B Miroux4, M E Symonds1*, and T Stephenson1
1 Centre for Reproduction and Early Life, University of Nottingham, Nottingham, United Kingdom
2 Department of Animal Sciences, University of Missouri, Missouri, USA
3 Food Science and Nutrition, The Hebrew University of Jerusalem, Rehovot, Israel
4 Faculte de Medecine, Centre National de la Recherche Scientifique, Paris, France
* To whom correspondence should be addressed. E-mail: michael.symonds{at}nottingham.ac.uk.
In the neonate, adipose tissue and the lung both undergo a rapid transition after birth, which results in dramatic changes in uncoupling protein abundance and glucocorticoid action. Leptin potentially mediates some of these adaptations and is known to promote the loss of uncoupling protein (UCP)1, but its effects on other mitochondrial proteins or glucocorticoid action are not known. We therefore determined the effects of acute and chronic administration of ovine recombinant leptin on brown adipose tissue (BAT) and/or lung in neonatal sheep. For the acute study, 8 pairs of 1-day old lambs received sequentially 10, 100 and 100 µg leptin or vehicle, before tissue sampling 4 hours from the start of the study, while in the chronic study, 9 pairs of 1-day old lambs received either 100 µg leptin or vehicle daily for 6 days, before tissue sampling on day 7. Acute leptin decreased the abundance of UCP2, glucocorticoid receptor and 11
hydroxysteroid dehydrogenase (HSD) type 1 mRNA, and increased 11HSD type 2 mRNA abundance in BAT, a pattern that was reversed with chronic leptin administration, which also diminished lung UCP2 protein abundance. In BAT, UCP2 mRNA abundance was positively correlated to plasma leptin and non-esterified fatty acids, and negatively correlated to mean colonic temperature in the leptin group at 7-days. In conclusion, leptin administration to the neonatal lambs causes differential effects on UCP2 abundance in BAT and lung. These effects may be important in the development of these tissues thereby optimising lung function and fat growth.
