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Glial cells as integrators of peripheral and central signals in the regulation of energy homeostasis

Nature Metabolism volume 4, pages 813–825 (2022)Cite this article

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Abstract

Communication between the periphery and the brain is key for maintaining energy homeostasis. To do so, peripheral signals from the circulation reach the brain via the circumventricular organs (CVOs), which are characterized by fenestrated vessels lacking the protective blood–brain barrier (BBB). Glial cells, by virtue of their plasticity and their ideal location at the interface of blood vessels and neurons, participate in the integration and transmission of peripheral information to neuronal networks in the brain for the neuroendocrine control of whole-body metabolism. Metabolic diseases, such as obesity and type 2 diabetes, can disrupt the brain-to-periphery communication mediated by glial cells, highlighting the relevance of these cell types in the pathophysiology of such complications. An improved understanding of how glial cells integrate and respond to metabolic and humoral signals has become a priority for the discovery of promising therapeutic strategies to treat metabolic disorders. This Review highlights the role of glial cells in the exchange of metabolic signals between the periphery and the brain that are relevant for the regulation of whole-body energy homeostasis.

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Fig. 1: The cross-talk between the brain and the peripheral organs via metabolic signals for energy homeostasis.
Fig. 2: Leptin and other circulating signals are transported from the periphery to hypothalamic areas around the 3V by tanycytes.
Fig. 3: Microglia in HFD-induced obesity and IL-1β/LPS-induced activation.

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Acknowledgements

This work was supported by the European Research Council (ERC) Synergy Grant WATCH (Well Aging and the Tanycytic Control of Health), No 810331 to R. N., V. P. and M. S.

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Authors and Affiliations

  1. Univ. Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, UMR-S1172, EGID, DISTALZ, Lille, France

    Sreekala Nampoothiri & Vincent Prevot

  2. Universidade de Santiago de Compostela-Instituto de Investigation Sanitaria, Santiago de Compostela, Spain

    Ruben Nogueiras

  3. CIBER Fisiopatologia de la Obesidad y Nutrition, Santiago de Compostela, Spain

    Ruben Nogueiras

  4. Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany

    Markus Schwaninger

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  4. Vincent Prevot
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S. N. and V. P. designed the structure of the Review. S. N. wrote the first draft. R. N., M. S. and V. P. discussed and edited the manuscript.

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Nampoothiri, S., Nogueiras, R., Schwaninger, M. et al. Glial cells as integrators of peripheral and central signals in the regulation of energy homeostasis. Nat Metab 4, 813–825 (2022). https://doi.org/10.1038/s42255-022-00610-z

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