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Selective Dependence of Intracerebroventricular Neuropeptide Y-Elicited Effects on Central Glucocorticoids¹

Laboratoires de Recherches Métaboliques (K.E.Z., I.C., B.J., F.R.-J.), Geneva University, School of Medicine, The Garvan Institute of Medical Research (A.S.), Diabetes Research Group, Sydney, New South Wales 2010, Australia; Department of Pharmacology and Clinical Pharmacology (J.R.), University of Turku, 20014 Turku, Finland

Address all correspondence and requests for reprints to: Katerina E. Zakrzewska or Isabelle Cusin, Laboratoires de Recherches Métaboliques, Hôpital cantonal universitaire de Genève, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. E-mail: katerina_z{at}hotmail.com

It has been reported that hyperphagia and excessive body weight gain of genetically obese rodents were abolished by adrenalectomy. High hypothalamic levels of neuropeptide Y (NPY) were found in obese rodents. A chronic intracerebroventricular (icv) infusion of NPY in normal rats was shown to produce most hormono-metabolic abnormalities of genetically obese animals, and to be inefficient in doing so in adrenalectomized (ADX) rats. The combined presence of NPY and of glucocorticoids thus appeared to be necessary for inducing obesity. This study, therefore, was aimed at determining the consequences of a chronic icv NPY infusion in ADX rats receiving or not icv glucocorticoids. It was found that the combined icv infusion of NPY and dexamethasone in ADX rats increased food intake, body weight, plasma insulin, leptin, and triglyceride levels relative to vehicle-infused ADX controls. The infusion of NPY alone, or of dexamethasone alone in ADX rats failed to produce these effects. In contrast, the icv infusion of NPY alone greatly decreased the expression of brown adipose tissue uncoupling protein-1 and -3. This was not modified by the superimposed infusion of dexamethasone. It is concluded that, although many of centrally elicited NPY effects require the central presence of glucocorticoids, those bearing on the inhibition of uncoupling proteins expression (energy dissipation) do not require central glucocorticoids.

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