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Coordinated changes in energy intake and expenditure following hypothalamic administration of neuropeptides involved in energy balance

International Journal of Obesity volume 33, pages 775–785 (2009)Cite this article

Abstract

Objective:

The hypothalamic control of energy balance is regulated by a complex network of neuropeptide-releasing neurons. Although the effect of these neuropeptides on individual aspects of energy homoeostasis has been studied, the coordinated response of these effects has not been comprehensively investigated. We have simultaneously monitored a number of metabolic parameters following intracerebroventricular (ICV) administration of 1 and 3 nmol of neuropeptides with established roles in the regulation of feeding, activity and metabolism. Ad libitum- fed rats received the orexigenic neuropeptides neuropeptide Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin-A. Overnight-food-deprived rats received an ICV injection of the anorectic peptides α-melanocyte-stimulating hormone (MSH), corticotrophin-releasing factor (CRF) or neuromedin U (NMU).

Results:

Our results reveal the temporal sequence of the effects of these neuropeptides on both energy intake and expenditure, highlighting key differences in their function as mediators of energy balance. NPY and AgRP increased feeding and decreased oxygen consumption, with the effects of AgRP being more prolonged. In contrast, orexin-A increased both feeding and oxygen consumption, consistent with an observed increase in activity. The potent anorexigenic effects of CRF were accompanied by a prolonged increase in activity, whereas NMU injection resulted in significant but short-lasting inhibition of food intake, ambulatory activity and oxygen consumption. α-MSH injection resulted in significant increases in both ambulatory activity and oxygen consumption, and reduced food intake following administration of 3 nmol of the peptide.

Conclusion:

We have for the first time, simultaneously measured several metabolic parameters following hypothalamic administration of a number of neuropeptides within the same experimental system. This work has shown the interrelated effects of these neuropeotides on activity, energy expenditure and food intake, thus facilitating comparison between the different hypothalamic systems.

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Acknowledgements

This research is funded by programme grants from the MRC (G7811974) and Wellcome Trust (072643/Z/03/Z) and by an EU FP6 Integrated Project Grant LSHM-CT-2003-503041. We are also grateful for the support from the NIHR Biomedical Research Centre funding scheme and an IMB Capacity building award. The CLAMS were purchased with joint funding from the Imperial College Strategic Infrastructure Fund and the MRC. KLS and KGM both hold BBSRC New Investigator Awards. The authors also thank Linton Instrumentation (Norfolk, UK) for their assistance in the installation and maintenance of the CLAMS.

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  1. N M Semjonous and K L Smith: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Investigative Medicine, Imperial College London, London, UK

    N M Semjonous, K L Smith, J R C Parkinson, D J L Gunner, Y-L Liu, K G Murphy, M A Ghatei, S R Bloom & C J Small

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  1. N M Semjonous
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Correspondence to S R Bloom.

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Semjonous, N., Smith, K., Parkinson, J. et al. Coordinated changes in energy intake and expenditure following hypothalamic administration of neuropeptides involved in energy balance. Int J Obes 33, 775–785 (2009). https://doi.org/10.1038/ijo.2009.96

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