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Effects of Obestatin on Energy Balance and Growth Hormone Secretion in Rodents

Department of Pharmacology (R.N., P.W., M.T., A.S., H.-G.J.), German Institute of Human Nutrition, D-14558 Potsdam-Rehbruecke, Germany; Department of Psychiatry (P.P., D.P.-T., T.R.C., M.T.), University of Cincinnati Genome Research Institute, Cincinnati, Ohio 45237; Department of Physiology (S.T., M.J.V., C.D.), University of Santiago de Compostela, 15781 Santiago de Compostela, Spain; Physiology and Animal Husbandry (M.A., W.L.), Institute of Animal Sciences, ETH Zurich, 8603 Schwerzenbach, Switzerland; Energy Balance and Obesity Division (S.M., A.M., L.M.W.), Rowett Research Institute, Aberdeen AB21 9SB, United Kingdom; and Department of Chemistry (R.D.), Indiana University, Bloomington, Indiana 47405

Address all correspondence and requests for reprints to: Prof. Carlos Diéguez, Department of Physiology, University of Santiago de Compostela, School of Medicine, C/S, Francisco 1, 15705 Santiago de Compostela, Spain. E-mail: fscadigo{at}usc.es.

Ghrelin stimulates food intake and adiposity and thereby increases body weight (BW) in rodents after central as well as peripheral administration. Recently, it was discovered that the gene precursor of ghrelin encoded another secreted and bioactive peptide named obestatin. First reports appeared to demonstrate that this peptide requires an amidation for its biological activity and acts through the orphan receptor, GPR-39. Obestatin was shown to have actions opposite to ghrelin on food intake, BW, and gastric emptying. In the present study, we failed to observe any effect of obestatin on food intake, BW, body composition, energy expenditure, locomotor activity, respiratory quotient, or hypothalamic neuropeptides involved in energy balance regulation. In agreement with the first report, we were unable to find any effect of obestatin on GH secretion in vivo. Moreover, we were unable to find mRNA expression of GPR-39, the putative obestatin receptor, in the hypothalamus of rats. Therefore, the results presented here do not support a role of the obestatin/GPR-39 system in the regulation of energy balance.

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