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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 10 4696-4701
Copyright © 2003 by The Endocrine Society

Oxyntomodulin Suppresses Appetite and Reduces Food Intake in Humans

Mark A. Cohen, Sandra M. Ellis, Carel W. Le Roux, Rachel L. Batterham, Adrian Park, Michael Patterson, Gary S. Frost, Mohammad A. Ghatei and Stephen R. Bloom

Departments of Metabolic Medicine (M.A.C., C.W.L.R., R.L.B., A.P., M.P., M.A.G., S.R.B.) and Dietetics (S.M.E., G.S.F.), Imperial College London, Hammersmith Hospital Campus, London, United Kingdom W12 0NN

Address all correspondence and requests for reprints to: Prof. Stephen R. Bloom, Department of Metabolic Medicine, Imperial College London at Hammersmith Campus, Du Cane Road, London, United Kingdom W12 0NN. E-mail: s.bloom{at}imperial.ac.uk.

Oxyntomodulin (OXM) is released from the gut postprandially, in proportion to energy intake, and circulating levels of OXM are elevated in several conditions associated with anorexia. Central injection of OXM reduces food intake and weight gain in rodents, suggesting that OXM signals food ingestion to hypothalamic appetite-regulating circuits. We investigated the effect of iv OXM (3.0 pmol/kg·min) on appetite and food intake in 13 healthy subjects (body mass index, 22.5 ± 0.9 kg/m2) in a randomized, double-blind, placebo-controlled, cross-over study. Infusion of OXM significantly reduced ad libitum energy intake at a buffet meal (mean decrease, 19.3 ± 5.6%; P < 0.01) and caused a significant reduction in scores for hunger. In addition, cumulative 12-h energy intake was significantly reduced by infusion of OXM (mean decrease, 11.3 ± 6.2%; P < 0.05). OXM did not cause nausea or affect food palatability. Preprandial levels of the appetite-stimulatory hormone, ghrelin, were significantly suppressed by OXM (mean reduction, 44 ± 10% of postprandial decrease; P < 0.0001). Elevated levels of endogenous OXM associated with disorders of the gastrointestinal tract may contribute to anorexia.

This work was supported by grants from the Medical Research Council, United Kingdom (to M.A.C.), and the Wellcome Trust (to C.L.R., R.L.B., and A.P.).

Abbreviations: GLP-1, Glucagon-like peptide-1; GLP-1R, glucagon-like peptide-1 receptor; OLI, oxyntomodulin-like immunoreactivity; OXM, oxyntomodulin; PYY, peptide YY; VAS, visual analog scales.




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