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Animal Models

Glucagon and GLP-1 inhibit food intake and increase c-fos expression in similar appetite regulating centres in the brainstem and amygdala

International Journal of Obesity volume 37, pages 1391–1398 (2013)Cite this article

Subjects

Abstract

Background:

Glucagon and glucagon-like peptide-1 (GLP-1) are evolutionarily related anorectic hormones. Glucagon also increases energy expenditure. The combination of glucagon and GLP-1 could cause weight loss through a simultaneous reduction in food intake and increased energy expenditure. However, the effect of combined administration of glucagon and GLP-1 on food intake and neuronal activation has not previously been studied. Furthermore, the effect of glucagon on neuronal activation in appetite regulating centres has not been assessed. Characterisation of the effects of glucagon when administered singly and in combination with GLP-1 on neuronal activation will be important for determining the mechanism of action of related potential antiobesity therapies.

Objectives:

To investigate the effects of peripherally administered GLP-1 and glucagon on food intake, neuronal activation and blood glucose in mice when administered individually and in combination.

Methodology:

Food intake, blood glucose and c-fos expression in the hypothalamus, amygdala and brainstem were measured in response to GLP-1 and glucagon, alone and in combination.

Results:

Peripherally administered GLP-1 and glucagon decreased food intake and increased c-fos expression in the brainstem and amygdala. Doses of GLP-1 and glucagon that individually did not significantly affect feeding, in combination were anorectic and stimulated neuronal activation in the area postrema (AP) and central nucleus of the amygdala. Combined administration of GLP-1 and glucagon prevented the acute hyperglycemic effect of glucagon alone.

Conclusion:

Anorectic doses of glucagon and GLP-1 induced similar patterns of c-fos expression. Combined administration of low dose GLP-1 and glucagon inhibited food intake and induced c-fos expression in the AP and amygdala. The combination of both hormones may offer the opportunity to utilise the beneficial effects of reduced food intake and increased energy expenditure, and may therefore be a potential treatment for obesity.

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Acknowledgements

We thank Dr Kevin Murphy for proof reading and comments made during manuscript preparation. The Section is funded by grants from the MRC, BBSRC, NIHR, an Integrative Mammalian Biology (IMB) Capacity Building Award, an FP7- HEALTH- 2009- 241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. In addition J.A.P is the recipient of a studentship from the Centre for Integrative Mammalian Physiology and Pharmacology; K.A.M is the recipient of a Wellcome PhD studentship; B.C.T.F is the recipient of an MRC Clinical Research Training Fellowship and an NIHR Clinical Lectureship; N.M.M is supported by an NIHR Clinical Senior Lectureship.

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  1. J A Parker and K A McCullough: These authors contributed equally to this work.

Authors and Affiliations

  1. Hammersmith Hospital, Section of Investigative Medicine, Imperial College London, London, UK

    J A Parker, K A McCullough, B C T Field, J S Minnion, N M Martin, M A Ghatei & S R Bloom

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  1. J A Parker
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Correspondence to S R Bloom.

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Parker, J., McCullough, K., Field, B. et al. Glucagon and GLP-1 inhibit food intake and increase c-fos expression in similar appetite regulating centres in the brainstem and amygdala. Int J Obes 37, 1391–1398 (2013). https://doi.org/10.1038/ijo.2012.227

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