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This Article Full Text Full Text (PDF) All Versions of this Article: 565/1/185    most recent jphysiol.2004.079079v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mühlhäusler, B. S. Articles by McMillen, I. C. Search for Related Content PubMed PubMed Citation Articles by Mühlhäusler, B. S. Articles by McMillen, I. C.

¹ Discipline of Physiology, Centre of the Early Origins of Adult Health, School of Molecular and Biomedical Science, University of Adelaide, Adelaide, Australia
² Energy Balance and Obesity Division, Rowett Research Institute, Bucksburn, Aberdeen, Scotland, UK
³ Department of Obstetrics & Gynecology, University of Adelaide, Adelaide, Australia
⁴ Department of Physiology, University of New England, Armidale, NSW, Australia

In the present study, our aim was to determine whether intrafetal glucose infusion increases fetal adiposity, synthesis and secretion of leptin and regulates gene expression of the ‘appetite regulatory’ neuropeptides neuropepetide Y (NPY), agouti-related peptide (AGRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) and receptors (leptin receptor (OB-Rb) and melancortin 3 receptor (MC3R)) within the fetal hypothalamus. Glucose (50% dextrose in saline) or saline was infused (7.5 ml h^–1) into fetal sheep between 130 and 140 days gestation (term = 150 ± 3 days gestation). Glucose infusion increased circulating glucose and insulin concentrations, mean lipid locule size (532.8 ± 3.3 µm²versus 456.7 ± 14.8 µm²) and total unilocular fat mass (11.7 ± 0.6 g versus 8.9 ± 0.6 g) of the perirenal fat depot. The expression of OB-Rb mRNA was higher in the ventromedial nucleus compared to the arcuate nucleus of the hypothalamus in both glucose and saline infused fetuses (F= 8.04; P < 0.01) and there was a positive correlation between expression of OB-Rb and MC3R mRNA in the arcuate nucleus (r= 0.81; P < 0.005). Glucose infusion increased mRNA expression for POMC, but not for the anorectic neuropeptide CART, or the orexigenic neuropeptides NPY and AGRP, in the arcuate nucleus of the fetal hypothalamus. These findings demonstrate that increased circulating glucose and insulin regulate gene expression of the neuropeptides within the fetal hypothalamus that are part of the neural network regulating energy balance in adult life.

(Received 10 November 2004; accepted after revision 14 January 2005; first published online 20 January 2005)
Corresponding author I. C. McMillen: Discipline of Physiology, The University of Adelaide, SA 5005 Australia. Email: caroline.mcmillen{at}adelaide.edu.au

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