Oxyntomodulin Suppresses Appetite and Reduces Food Intake in Humans

Department of Metabolic Medicine, Imperial College London, Hammersmith Hospital Campus, London, United Kingdom W12 0NN.
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 10/2003; 88(10):4696-701. DOI: 10.1210/jc.2003-030421
Source: PubMed


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/m(2)) 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.

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    • "Actions of OXM include inhibition of basal and postprandial gastric acid secretion , gastroduodenal motility and gastric emptying ( Schjoldager et al . , 1989 ) . Furthermore , OXM reduces food intake in rats ( Dakin et al . , 2001 ) and P a g e | 39 humans ( Cohen et al . , 2003 ) . In obese non - diabetic volunteers , preprandial subcutaneous administration of OXM resulted in significant weight loss over a four - week study period ( Wynne et al . , 2005 ) . A cumulative effect on food intake"

    Full-text · Thesis · Feb 2015
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    • "OXM administration in animals and humans causes weight loss by reducing food intake in combination with increasing energy expenditure. Thus, the development of long-acting analogs of OXM is an exciting new therapeutic avenue for addressing the global obesity epidemic [200] [201] [202] Recently, it has been demonstrated that Preproghrelin may undergo an additional proteolytic cleavage, generating a 23-amino acid peptide named Obestatin. Unlike Ghrelin, Obestatin has anorexigenic effects and reduces gastric emptying and jejunal contractions, counteracting weight gain; however, some studies have not reproduced these results [203] [204]. "

    Full-text · Article · Dec 2014
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    • "Recently, Tan and colleagues reported an inhibitory effect on plasma levels of the anorexigenic hormone ghrelin in humans during short-term infusion of GLP-1 and glucagon [68]. While part of this effect could be mediated by insulin stimulation, central administration of OXM suppresses circulating ghrelin-like immunoreactivity in rodents [69] and intravenous infusion of OXM at a dose that did not stimulate insulin secretion lowered ghrelin in humans [37]. Thus, it appears that while GLP-1 suppresses plasma ghrelin in humans via insulin secretion in the late postprandial period [70], OXM and GLP-1/glucagon co-administration exert a ghrelin-lowering effect independent of insulin (Figure 2). "
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    ABSTRACT: Oxyntomodulin (OXM) is a peptide hormone released from the gut in post-prandial state that activates both the glucagon-like peptide-1 receptor (GLP1R) and the glucagon receptor (GCGR) resulting in superior body weight lowering to selective GLP1R agonists. OXM reduces food intake and increases energy expenditure in humans. While activation of the GCGR increases glucose production posing a hyperglycemic risk, the simultaneous activation of the GLP1R counteracts this effect. Acute OXM infusion improves glucose tolerance in T2DM patients making dual agonists of the GCGR and GLP1R new promising treatments for diabetes and obesity with the potential for weight loss and glucose lowering superior to that of GLP1R agonists.
    Full-text · Article · Jun 2014 · Molecular Metabolism
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