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The metabolic role of vagal afferent innervation

Nature Reviews Gastroenterology & Hepatology volume 15, pages 625–636 (2018)Cite this article

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Abstract

The regulation of energy and glucose balance contributes to whole-body metabolic homeostasis, and such metabolic regulation is disrupted in obesity and diabetes. Metabolic homeostasis is orchestrated partly in response to nutrient and vagal-dependent gut-initiated functions. Specifically, the sensory and motor fibres of the vagus nerve transmit intestinal signals to the central nervous system and exert biological and physiological responses. In the past decade, the understanding of the regulation of vagal afferent signals and of the associated metabolic effect on whole-body energy and glucose balance has progressed. This Review highlights the contributions made to the understanding of the vagal afferent system and examines the integrative role of the vagal afferent in gastrointestinal regulation of appetite and glucose homeostasis. Investigating the integrative and metabolic role of vagal afferent signalling represents a potential strategy to discover novel therapeutic targets to restore energy and glucose balance in diabetes and obesity.

Key points

  • Vagal afferent nerve terminals innervate layers of the gastrointestinal wall to sense nutrient-related hormonal and/or mechanical signals and trigger neuronal transmission to the central nervous system to affect metabolic homeostasis.

  • Nutrient-dependent hormonal and mechanical stimulation in the stomach and the intestine regulate feeding through the vagal afferent network.

  • Nutrient-dependent hormonal stimulation in the intestine regulates glucose homeostasis through the vagal afferent network.

  • Manipulating gut nutrient-dependent and vagal-dependent afferent firing represents a potential novel therapeutic strategy for obesity and diabetes.

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Fig. 1: Subdiaphragmatic vagal afferent innervation and gross anatomical organization of the nodose ganglia.
Fig. 2: Distribution of the vagal afferent nerve terminals that respond to hormonal and mechanically dependent signals.
Fig. 3: Schematic diagram for the proposed signal transmission pathways for the vagal afferent system.
Fig. 4: Role of the gut vagal afferent system in feeding and glucose regulation.

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Acknowledgements

T.M.Z.W. is supported by a postdoctoral fellowship from the Banting and Best Diabetes Centre. H.J.D. is supported by Canadian Institutes of Health Research (CIHR) and Diabetes Canada postdoctoral fellowships. Part of the work discussed in this Review conducted by the Lam laboratory was supported by a CIHR Foundation Grant to T.K.T.L. (FDN-143204). T.K.T.L. holds the John Kitson McIvor (1915–1942) Endowed Chair in Diabetes Research and the Canada Research Chair in Obesity at the Toronto General Hospital Research Institute and the University of Toronto.

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  1. Toronto General Hospital Research Institute, UHN, Toronto, Canada

    T. M. Zaved Waise, Helen J. Dranse & Tony K. T. Lam

  2. Departments of Physiology, University of Toronto, Toronto, Canada

    Tony K. T. Lam

  3. Departments of Medicine, University of Toronto, Toronto, Canada

    Tony K. T. Lam

  4. Banting and Best Diabetes Centre, University of Toronto, Toronto, Canada

    Tony K. T. Lam

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Waise, T.M.Z., Dranse, H.J. & Lam, T.K.T. The metabolic role of vagal afferent innervation. Nat Rev Gastroenterol Hepatol 15, 625–636 (2018). https://doi.org/10.1038/s41575-018-0062-1

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