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Inflammation and resolution in obesity

Nature Reviews Endocrinology volume 21, pages 45–61 (2025)Cite this article

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Abstract

Inflammation is an essential physiological defence mechanism, but prolonged or excessive inflammation can cause disease. Indeed, unresolved systemic and adipose tissue inflammation drives obesity-related cardiovascular disease and type 2 diabetes mellitus. Drugs targeting pro-inflammatory cytokine pathways or inflammasome activation have been approved for clinical use for the past two decades. However, potentially serious adverse effects, such as drug-induced weight gain and increased susceptibility to infections, prevented their wider clinical implementation. Furthermore, these drugs do not modulate the resolution phase of inflammation. This phase is an active process orchestrated by specialized pro-resolving mediators, such as lipoxins, and other endogenous resolution mechanisms. Pro-resolving mediators mitigate inflammation and development of obesity-related disease, for instance, alleviating insulin resistance and atherosclerosis in experimental disease models, so mechanisms to modulate their activity are, therefore, of great therapeutic interest. Here, we review current clinical attempts to either target pro-inflammatory mediators (IL-1β, NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome, tumour necrosis factor (TNF) and IL-6) or utilize endogenous resolution pathways to reduce obesity-related inflammation and improve cardiometabolic outcomes. A remaining challenge in the field is to establish more precise biomarkers that can differentiate between acute and chronic inflammation and to assess the functionality of individual leukocyte populations. Such advancements would improve the monitoring of drug effects and support personalized treatment strategies that battle obesity-related inflammation and cardiometabolic disease.

Key points

  • Chronic unresolved systemic and adipose tissue inflammation drives obesity-related cardiometabolic disease.

  • Drugs targeting pro-inflammatory cytokines, or inflammasome activation, are approved for clinical use but can elicit serious adverse effects (such as weight gain and increased susceptibility to infections), hampering their clinical implementation.

  • The resolution phase of inflammation is an active process regulated by specialized pro-resolving mediators. These mediators mitigate obesity-related inflammation and systemic disease in experimental models and are of therapeutic interest.

  • The field lacks biomarkers that can differentiate between acute and chronic inflammation and assess the functionality of individual leukocyte populations, which would improve personalized treatment strategies and support drug monitoring.

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Fig. 1: Specialized pro-resolving mediator synthesis pathways.
Fig. 2: Anti-inflammatory therapeutic strategies under investigation to reduce obesity-related inflammation and disease burdens.
Fig. 3: Pro-resolving therapeutic strategies under investigation to reduce obesity-related inflammation and disease burdens.
Fig. 4: Timing is crucial to the inflammatory process.

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Acknowledgements

The work of E.B. is supported by the European Research Council (ERC-StG no. 804418), Independent Research Fund Denmark (DFF number 3165-00026B), Aarhus University Research Foundation (AUFF-E-2022-7-8), Novo Nordisk Foundation (NNF22OC0079363), the Swedish Research Council (VR 2023-02627), the Swedish state’s ALF-agreement (ALFGBG-978978), and Regionala FoU-medel Västra Götalandsregionen (OLG-2023-02-22). The authors thank S. Tavajoh and A. Harazin for their valuable input while assembling the manuscript.

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  1. Department of Clinical Immunology and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden

    Matúš Soták & Emma Börgeson

  2. Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark

    Madison Clark, Bianca E. Suur & Emma Börgeson

  3. Department of Biomedicine, Aarhus University, Aarhus, Denmark

    Madison Clark, Bianca E. Suur & Emma Börgeson

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Soták, M., Clark, M., Suur, B.E. et al. Inflammation and resolution in obesity. Nat Rev Endocrinol 21, 45–61 (2025). https://doi.org/10.1038/s41574-024-01047-y

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