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This version published online on October 5, 2006
Endocrinology, doi:10.1210/en.2006-0918
A more recent version of this article appeared on January 1, 2007
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Submitted on July 10, 2006
Accepted on September 25, 2006

Ontogenic loss of brown adipose tissue sensitivity to {beta}-adrenergic stimulation in the ovine

MICHAEL A LOMAX*, FOUZIA SADIQ, GEORGIOS KARAMANLIDIS, ANGELIKI KARAMITRI, PAUL TRAYHURN, and DAVID G. HAZLERIGG

Division of Biomedical Science, Imperial College, Wye Campus, Ashford, Kent TN25 5AH, UK. Division of Molecular Biology, Imperial College, Wye Campus, Ashford, Kent TN25 5AH. Liverpool Centre for Nutritional Genomics, Obesity Biology Unit, School of Clinical Sciences, University of Liverpool, University Clinical Departments, Liverpool L693GA,UK. School of Biological Sciences, University of Aberdeen, Aberdeen, AB24 5UH, UK

* To whom correspondence should be addressed. E-mail: m.lomax{at}imperial.ac.uk.

In ruminants and other large animals expression of uncoupling protein-1 (UCP1) in brown adipose tissue (BAT) is confined to the perinatal period when it plays a key role in non-shivering thermogenesis. This study determined whether loss of expression of the BAT phenotype was due to reduced response to a {beta}-agonist, isoprenaline, and expression of the peroxisome proliferator activated receptor family (PPAR{alpha}, PPAR{gamma}, PGC-1{alpha}) which regulate UCP1 gene expression. Perirenal adipose tissue (PAT) was sampled from ovine fetuses, newborn lambs, and lambs on days 1, 5, 7 and 21 of life. UCP1 mRNA and protein in PAT increased from day 123 of fetal life to reach a maximum at birth followed by a rapid decrease over the first 5 days of life. Expression of the coactivator, PGC-1{alpha} and PPAR {alpha}, peaked between fetal day 123 and birth, and then declined to undetectable levels in the first days of life. In vivo administration of isoprenaline, was able to induce expression of UCP1, PGC-1{alpha} and PPAR{alpha} in brown adipose tissue up to 5 days of age, but thereafter was ineffective. In vitro addition of {beta}-receptor, PPAR{alpha} and PPAR{gamma} agonists were unable to overcome the suppression of UCP1, PPAR{alpha} and PPAR{gamma} expression observed in differentiated adipocytes prepared from 30day compared with 1 days old lambs. These data are consistent with a model in which post natal loss of UCP1 expression and {beta}-adrenergic induction of the brown adipocyte phenotype is due to loss of expression of PGC-1{alpha} and PPAR{alpha}.


Key words: Uncoupling protein-1 • development • {beta}-agonist • sheep




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