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Title

The melanocortin agonist Melanotan-II reduces the orexigenic and adipogenic effects of neuropeptide Y (NPY) but does not affect the NPY-driven suppressive effects on the gonadotropic and somatotropic axes in the male rat

Authors
Raposinho, Paula
White, R B
Published in Journal of Neuroendocrinology. 2003, vol. 15, no. 2, p. 173-81
Abstract Neuropeptide Y (NPY) is a strong orexigenic neurotransmitter also known to modulate several neuroendocrine axes. alpha-Melanocyte-stimulating hormone (MSH) is an essential anorectic neuropeptide, acting on hypothalamic MC3/4 receptor subtypes. When given as an intracerebroventricular bolus injection, Melanotan-II (MT-II), a non selective MC receptor agonist, inhibits feeding, suppresses the NPY orexigenic action, and reduces basal insulinaemia. We evaluated the effects of a 7-day central infusion of MT-II (15 nmol/day) given either alone or in association with NPY (5 nmol/day) in male Sprague-Dawley rats. MT-II produced almost full anorexia for 1-2 days but then feeding gradually returned to normal despite continued MT-II infusion. When coinfused with NPY, MT-II also produced the same initial anorectic episode but then maintained feeding to upper normal levels, thus cancelling the hyperphagia driven by NPY. Whereas NPY infusion produced a doubling of fat pad weight, MT-II reduced adiposity by a factor of two compared to pair-fed rats, and vastly curtailed the NPY-driven increase in fat pad weight. MT-II infusion also significantly curtailed the NPY-induced rise in insulin and leptin secretions. NPY infusion significantly inhibited hypothalamic pro-opiomelanocortin mRNA expression, most likely cancelling the alpha-MSH anorectic activity. As expected from previous studies, chronic NPY infusion strongly inhibited both the gonadotropic and somatotropic axes, and coinfusion of MT-II did not reverse these NPY-driven effects, in sharp contrast with that seen for the metabolic data. MT-II infusion alone had little effect on these axes. In conclusion, chronic MT-II infusion generated a severe but transient reduction in feeding, suggesting an escape phenomenon, and clearly reduced fat pad size. When coinfused with NPY, MT-II was able to cancel most of the NPY effects on feeding, but not those on the neuroendocrine axes. It appears therefore that, as expected, NPY and alpha-MSH closely interact in the control of feeding, whereas the neural pathways by which NPY affects growth and reproduction are distinct and not sensitive to MC peptide modulation.
Keywords Adipocytes/physiologyAdipose Tissue/anatomy & histologyAnimalsCarrier Proteins/physiologyDrinking/drug effectsDrug InteractionsEating/drug effectsGene Expression/drug effectsGonadal Steroid Hormones/physiologyGrowth Hormone-Releasing Hormone/geneticsHypothalamus/drug effects/physiologyInsulin/bloodInsulin-Like Growth Factor I/genetics/metabolismIntracellular Signaling Peptides and ProteinsLeptin/bloodMaleNeuropeptide Y/genetics/pharmacologyNeuropeptides/physiologyObesity/physiopathologyPeptides, Cyclic/pharmacologyPro-Opiomelanocortin/geneticsRatsRats, Sprague-DawleyWeight Gain/drug effectsAlpha-MSH/agonists/analogs & derivatives/pharmacology
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PMID: 12535159
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RAPOSINHO, Paula, WHITE, R B, AUBERT, Michel. The melanocortin agonist Melanotan-II reduces the orexigenic and adipogenic effects of neuropeptide Y (NPY) but does not affect the NPY-driven suppressive effects on the gonadotropic and somatotropic axes in the male rat. In: Journal of Neuroendocrinology, 2003, vol. 15, n° 2, p. 173-81. https://archive-ouverte.unige.ch/unige:55261

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Deposited on : 2015-04-08

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