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  • Review Article
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The autonomic nervous system in the regulation of glucose and lipid metabolism

Nature Reviews Endocrinology (2026)Cite this article

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Abstract

The autonomic nervous system is a crucial mediator between the central nervous system and peripheral tissues and is essential for maintaining homeostasis. In this Review, we discuss the bidirectional communication between the autonomic nervous system and metabolic tissues in humans, focusing on the coordination of systemic glucose and lipid metabolism through autonomic signalling across changing physiological states. We also discuss the crosstalk between autonomic and immune pathways and its relevance for metabolic control. An overview of current methodologies to assess autonomic function in humans shows that quantifying organ-specific autonomic outflows remains challenging. Chronic disturbances in autonomic regulation are increasingly recognized as contributors to metabolic diseases such as obesity and type 2 diabetes mellitus. Hence, emerging therapeutic strategies targeting autonomic function could offer promising opportunities to improve metabolic health. Progress will depend on the development of tools to selectively assess autonomic input to individual metabolic organs. Addressing high inter-individual variability and capturing the temporal dynamics of organ-specific autonomic regulation will be essential for advancing mechanistic insights, ultimately enabling clinical translation.

Key points

  • The autonomic nervous system regulates glucose metabolism via coordinated brain–periphery signalling, regulating insulin secretion, hepatic glucose production, adipose lipolysis and skeletal muscle glucose uptake among other functions.

  • Both sympathetic and parasympathetic branches of the autonomic nervous system contribute to glucose homeostasis in a context-dependent manner, shaped by feeding status, stress, circadian rhythm and immune interactions.

  • Organ-specific autonomic inputs are challenging to assess; current measures (for example, heart rate variability) provide only partial insights into metabolic autonomic regulation.

  • Chronic autonomic imbalance, especially increased sympathetic tone, is implicated in the development of obesity, insulin resistance and type 2 diabetes mellitus.

  • Emerging interventions, including lifestyle changes, pharmacotherapy and device-based neuromodulation, offer promising approaches to restore autonomic balance and improve metabolic outcomes.

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Fig. 1: Efferent regulation of metabolic organ function by the ANS.
Fig. 2: Tissue-specific distribution and effects of autonomic receptors on metabolic cell function.

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Acknowledgements

The authors acknowledge the support of an ERC Consolidator grant (CrossPeriBrain, Project 101125605 to M.H.).

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Authors and Affiliations

  1. Division of Endocrinology and Diabetology, Department of Internal Medicine I, Ulm University Hospital, Ulm, Germany

    Sabrina Wangler, Matthew Ennis, Ratika Sehgal & Martin Heni

  2. Department of Psychosomatic Medicine and Psychotherapy, Ulm University Hospital, Ulm, Germany

    Marc N. Jarczok

  3. Medical Psychology and Medical Sociology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany

    Benedict Herhaus

  4. German Center for Diabetes Research (DZD), Neuherberg, Germany

    Róbert Wagner

  5. Institute for Clinical Diabetology, German Diabetes Center (DDZ), Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany

    Róbert Wagner

  6. Department of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine-University and University Hospital Düsseldorf, Düsseldorf, Germany

    Róbert Wagner

  7. Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany

    Martin Heni

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All authors reviewed data for the article. All authors contributed substantially to discussion of the content. S.W., M.N.J., M.E., R.S. and M.H. wrote the article. All authors reviewed and/or edited the manuscript and approved the final version before submission.

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Competing interests

M.N.J. reports scientific consultation work for LaVita GmbH. R.W. reports receiving lecture fees from Boehringer Ingelheim, Eli Lilly, Novo Nordisk and Sanofi-Aventis, and has served on the advisory board for Akcea Therapeutics, Daiichi Sankyo, Eli Lilly, Novo Nordisk and Sanofi-Aventis. M.H. reports receiving lecture fees from Amryt/Chiesi, AstraZeneca, Bayer, Boehringer Ingelheim, Daichii Sankyo, Lilly, Novartis, Novo Nordisk and Sanofi-Aventis. He has also served on advisory boards for Amryt/Chiesi and Boehringer Ingelheim. He is currently a board member of the German Diabetes Association. The other authors declare no competing interests.

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Wangler, S., Jarczok, M.N., Ennis, M. et al. The autonomic nervous system in the regulation of glucose and lipid metabolism. Nat Rev Endocrinol (2026). https://doi.org/10.1038/s41574-025-01221-w

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