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  • Review Article
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GLP-1 and energy balance: an integrated model of short-term and long-term control

Nature Reviews Endocrinology volume 7, pages 507–516 (2011)Cite this article

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Abstract

Glucagon-like peptide 1 (GLP-1), a peptide secreted from the intestine in response to nutrient ingestion, is perhaps best known for its effect on glucose-stimulated insulin secretion. GLP-1 is also secreted from neurons in the caudal brainstem, and it is well-established that, in rodents, central administration of GLP-1 potently reduces food intake. Over the past decade, GLP-1 has emerged not only as an essential component of the system that regulates blood glucose levels but also as a viable therapeutic target for the treatment of type 2 diabetes mellitus. However, although GLP-1 receptor agonists are known to produce modest but statistically significant weight loss in patients with diabetes mellitus, our knowledge of how endogenous GLP-1 regulates food intake and body weight remains limited. The purpose of this Review is to discuss the evolution of our understanding of how endogenous GLP-1 modulates energy balance. Specifically, we consider contributions of both central and peripheral GLP-1 and propose an integrated model of short-term and long-term control of energy balance. Finally, we discuss this model with respect to current GLP-1-based therapies and suggest ongoing research in order to maximize the effectiveness of GLP-1-based treatment of obesity.

Key Points

  • Animal studies suggest that endogenous, central glucagon-like peptide 1 (GLP-1) regulates both short-term and long-term energy balance, potentially via activation of hindbrain and hypothalamic GLP-1 receptors (GLP1R), respectively

  • Endogenous peripheral GLP-1 may limit meal size by activation of GLP1R on local vagal afferent nerves and stimulation of a gut–brain feedback loop

  • Increasing GLP1R activity by administering GLP-1 receptor agonists reduces food intake and promotes weight loss in humans, but the extent to which endogenous GLP-1 regulates energy balance in humans remains unknown

  • Although diabetes mellitus and obesity appear to be associated with altered GLP-1 system activity, GLP1R agonists retain their efficacy in these contexts, making them a viable therapeutic tool

  • A better understanding of how endogenous central and peripheral GLP-1 regulate energy balance has the potential to maximize our application of GLP-1-based therapies for the treatment of obesity

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Figure 1: Model of GLP-1 physiology.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Cincinnati, 2170 East Galbraith Road, Cincinnati, 45237, OH, USA

    Jason G. Barrera, Darleen A. Sandoval, David A. D'Alessio & Randy J. Seeley

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  4. Randy J. Seeley
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All authors researched the data for the article, provided a substantial contribution to discussions of the content, contributed equally to writing the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Randy J. Seeley.

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Competing interests

D. A. Sandoval declares an association with the following company: Ethicon (research support). D. A. D'Alessio declares an association with the following companies: Amylin (research support, consulting), Johnson and Johnson (research support, scientific advisory boards, consulting), MannKind (research support), Merck (consulting), Novo Nordisk (scientific advisory board), Sanofi-Aventis (research support), Takeda (consulting). R. J. Seeley declares an association with the following companies: Alkermes (consulting), Amylin (consulting, research support, speakers bureau), Eli Lilly (scientific advisory board, speakers bureau), Johnson and Johnson (research support, scientific advisory board, consulting), MannKind (research support), Merck (scientific advisory board, speakers bureau), Novo Nordisk (speakers bureau, scientific advisory board), Roche (consulting, research support), Zafgen (scientific advisory board, equity stake (<1%), research support. J. G. Barrera declares no competing interests.

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Barrera, J., Sandoval, D., D'Alessio, D. et al. GLP-1 and energy balance: an integrated model of short-term and long-term control. Nat Rev Endocrinol 7, 507–516 (2011). https://doi.org/10.1038/nrendo.2011.77

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