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Am J Physiol Endocrinol Metab 289: E1093-E1100, 2005. First published August 9, 2005; doi:10.1152/ajpendo.00228.2005
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Differential effects of leptin administration on the abundance of UCP2 and glucocorticoid action during neonatal development

M. G. Gnanalingham,1 A. Mostyn,1 R. Webb,1 D. H. Keisler,2 N. Raver,3 M. C. Alves-Guerra,4 C. Pecqueur,4 B. Miroux,4 M. E. Symonds,1 and T. Stephenson1

1Centre for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, Nottingham, United Kingdom; 2Department of Animal Sciences, University of Missouri, Columbia, Missouri; 3Institute of Biochemistry, Food Science and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences, The Hebrew University of Jerusalem, Rehovot, Israel; and 4Faculté de Médecine Necker-Enfants-Malades, Paris, France

Submitted 13 May 2005 ; accepted in final form 1 August 2005

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, eight pairs of 1-day-old lambs received, sequentially, 10, 100, and 100 µg of leptin or vehicle before tissue sampling 4 h from the start of the study, whereas in the chronic study, nine pairs of 1-day-old lambs received 100 µg of leptin or vehicle daily for 6 days before tissue sampling on day 7. Acute leptin decreased the abundance of UCP2, glucocorticoid receptor, and 11{beta}-hydroxysteroid dehydrogenase (11{beta}-HSD) type 1 mRNA and increased 11{beta}-HSD 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 nonesterified 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 optimizing lung function and fat growth.

lung; neonate; mitochondria; uncoupling protein-2



Address for reprint requests and other correspondence: M. E. Symonds, Academic Division of Child Health, School of Human Development, Queen’s Medical Centre, University Hospital, Nottingham NG7 2UH, UK (e-mail: michael.symonds{at}nottingham.ac.uk)







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