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Long-Term Alterations in Adiposity Affect the Expression of Melanin-Concentrating Hormone and Enkephalin But Not Proopiomelanocortin in the Hypothalamus of Ovariectomized Ewes¹

Prince Henry’s Institute of Medical Research (B.A.H., A.R., I.J.C.) and Department of Physiology (A.J.T.), Monash University, Clayton, Victoria 3168, Australia; Agriculture Victoria (F.R.D.), Victorian Institute of Animal Science, Werribee, Victoria 3030, Australia; and Animal Science (D.B., G.B.M.), Faculty of Agriculture, University of Western Australia, Nedlands, Western Australia 6009, Australia

Address all correspondence and requests for reprints to: Iain J. Clarke, Ph.D., Prince Henry’s Institute, Monash Medical Centre, Level 4, Block E, 246 Clayton Road, P.O. Box 5152, Victoria 3168, Australia. E-mail: iain.clarke{at}med.monash.edu.au

We have developed a ruminant model to study long-term alterations in adiposity on the expression of appetite-regulating peptides in the hypothalamus. In this model endocrine and metabolic status are fully defined as well as body composition. The current study sought to define the effects of altered adiposity on the expression of genes for neuropeptide Y (NPY), POMC, enkephalin (ENK), and melanin-concentrating hormone (MCH). Ovariectomized ewes with high (60 ± 1 kg) (FAT) or low (37 ± 3 kg) body weights (THIN) were blood sampled every 10 min for 8 h to determine metabolic and endocrine status. The animals were then killed and the brains perfused for in situ hybridization. Body composition analysis was performed on the carcass using dual energy x-ray absorptiometry; this indicated that the FAT animals were 36 ± 1% fat, whereas the THIN animals were 15 ± 2% fat. The LH interpulse interval was lower and mean GH concentrations were higher in the THIN animals; cortisol and TSH levels were not different between the two groups but free T₄ and free T₃ levels were lower; the FT₃:FT₄ ratio was higher in THIN ewes. Levels of insulin, lactate, and nonesterified fatty acids were lower in the THIN group, and plasma glucose and urea concentrations were similar in THIN and FAT animals. Levels of gene expression of NPY and MCH were higher in THIN ewes. POMC expression was similar in the two groups. In the THIN animals, ENK expression was lower in the paraventricular and ventromedial nuclei but higher in the periventricular region. In conclusion, we have shown that alterations in adiposity influence the expression of appetite-regulating peptides in the absence of ovarian steroids. The appetite stimulators, NPY and MCH, appear to be involved in the metabolic response to altered adiposity, whereas ENK in the periventricular region may be linked to the secretion of GH and possibly LH. Our results suggest that altered expression of appetite- regulating peptides can be linked with the endocrine and metabolic adaptations that occur with long-term changes in adiposity.

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