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  • Review Article
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Obesity-induced inflammation: connecting the periphery to the brain

Nature Metabolism volume 6, pages 1237–1252 (2024)Cite this article

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Abstract

Obesity is often associated with a chronic, low-grade inflammatory state affecting the entire body. This sustained inflammatory state disrupts the coordinated communication between the periphery and the brain, which has a crucial role in maintaining homeostasis through humoural, nutrient-mediated, immune and nervous signalling pathways. The inflammatory changes induced by obesity specifically affect communication interfaces, including the blood–brain barrier, glymphatic system and meninges. Consequently, brain areas near the third ventricle, including the hypothalamus and other cognition-relevant regions, become susceptible to impairments, resulting in energy homeostasis dysregulation and an elevated risk of cognitive impairments such as Alzheimer’s disease and dementia. This Review explores the intricate communication between the brain and the periphery, highlighting the effect of obesity-induced inflammation on brain function.

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Fig. 1: Periphery–brain interactions and immune responses in obesity.
Fig. 2: Brain ‘frontiers’.
Fig. 3: Obesity and hypothalamic dysfunction.
Fig. 4: Timeline of key discoveries in the body–brain (hypothalamus) interactions and obesity-related inflammation.

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Acknowledgements

We thank C. Holleman for comments. This research is supported by funding from the DZD, the German Research Foundation DFG under Germany’s Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145 SyNergy – ID 390857198), and Helmholtz Association - Initiative and Networking Fund. The funders had no role in decision to publish or prepare this work.

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Authors and Affiliations

  1. Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, Neuherberg, Germany

    Ophélia Le Thuc & Cristina García-Cáceres

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

    Ophélia Le Thuc & Cristina García-Cáceres

  3. Medizinische Klinik und Poliklinik IV, Klinikum der Universität, Ludwig-Maximilians-Universität München, Munich, Germany

    Cristina García-Cáceres

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O.L.T. and C.G.-C. conceptualized the content, wrote, edited and revised the original draft. Both authors have reviewed and approved the final version of the manuscript for publication.

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Correspondence to Cristina García-Cáceres.

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Le Thuc, O., García-Cáceres, C. Obesity-induced inflammation: connecting the periphery to the brain. Nat Metab 6, 1237–1252 (2024). https://doi.org/10.1038/s42255-024-01079-8

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