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Bariatric Surgery

The long-term effect of metabolic bariatric surgery on innate immune cell phenotype and function

International Journal of Obesity volume 49, pages 2473–2483 (2025)Cite this article

Subjects

Abstract

Objectives

Obesity is an important risk factor for atherosclerotic cardiovascular disease. This cardiovascular risk remains increased even after substantial weight loss by bariatric surgery. Innate immune cells are important regulators of atherogenesis and can adopt a long-term hyperinflammatory phenotype via epigenetic reprogramming, called “trained immunity”. In this translational observational case-cohort study, we investigated the persistence of innate immune cell hyperresponsiveness following bariatric surgery, and explored the potential contribution of adipose tissue in ex vivo models.

Subjects/methods

In a cohort of 27 patients with obesity blood was drawn before and six months after bariatric surgery, and compared to 20 healthy subjects with normal body weight. We assessed monocytes using flow cytometry, functional assays, and RNA sequencing and chromatin immunoprecipitation. In an accompanying series of in vitro studies, healthy donor monocytes were exposed for 24 h to adipose tissue obtained from patients with obesity during bariatric surgery. Cytokine production capacity was assessed after one week.

Results

In our case-cohort study, although leukocyte numbers and systemic inflammatory markers such as hs-CRP decreased after bariatric surgery to the level of normal weight control subjects, the hyperresponsive pro-inflammatory monocyte phenotype was only partially reverted six months after bariatric surgery, which aligned with the RNA expression profiles. Exposure of monocytes to adipose tissue obtained from patients with obesity induces a persistent augmented cytokine production capacity.

Conclusions

Although in patients with obesity, six months after bariatric surgery systemic inflammatory markers and leukocyte numbers are decreased to the levels observed in healthy lean subjects, there is still a residual functional and transcriptional hyper-inflammatory monocyte phenotype. This might be caused, at least in part, by the capacity of adipose tissue to induce long-term pro-inflammatory effects in monocytes. These finding help to understand the long-term effects of obesity and bariatric surgery on cardiovascular health.

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Fig. 1: Differences in circulating immune cell phenotype after bariatric surgery.
Fig. 2: The increased PBMC cytokine production capacity in patients with obesity is not completely resolved after bariatric surgery.
Fig. 3: Monocytes from patients with severe obesity have a distinct transcriptional profile compared to controls, which only partly reverses upon bariatric surgery.
Fig. 4: Systemic inflammation is reduced after bariatric surgery.
Fig. 5: Subcutaneous and visceral adipose tissue induce trained immunity in healthy human monocytes.

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Data availability

All RNA sequencing datasets from the patients, and from the ex vivo studies is available in the Radboud Data Repository: https://doi.org/10.34973/f93x-3246 The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request: Niels P. Riksen (niels.riksen@radboudumc.nl).

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Acknowledgements

The authors thank Jessica Snabel for technical assistance with the plasma analyses. NPR, MGN, and LABJ received a CVON grant from the Dutch Cardiovascular Alliance (DCVA) and Dutch Heart Foundation (CVON2018-27; IN CONTROL II). NPR was recipient of a grant of the ERA-CVD Joint Transnational Call 2018 supported by the Dutch Heart Foundation (JTC2018, project MEMORY; 2018T093) SB is supported by the Dutch Heart Foundation (2018T028). MGN was supported by an ERC Advanced Grant (#833247) and a Spinoza grant of the Netherlands Organization for Scientific Research. YL was supported by an ERC starting Grant (948207) and a Radboud University Medical Center Hypatia Grant. AJK was supported by a grant of the Rijnstate-Radboudumc Promotion Fund. RK and FS received support from TNO’s Research programs Biomedical Health (PMC13) and seed-ERP Brain-Power. This study was performed in collaboration with the Netherlands Organisation for Applied Scientific Research (TNO) Metabolisch Health Research (Leiden, the Netherlands) with support from the Shared Research Program GLoBAL, an initiative of the Radboudumc, Rijnstate Hospital and TNO.

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands

    Julia van Tuijl, Wieteke Broeders, Benjamin Cossins, Liesbeth van Emst, Rinke Stienstra, Leo A. B. Joosten, Mihai G. Netea, Siroon Bekkering & Niels P. Riksen

  2. Department of Medical Imaging, Anatomy, Radboud Alzheimer Center, Donders Institute for Brain Cognition and Behaviour, Center of Medical Neuroscience, Nijmegen, the Netherlands

    Debby Vreeken, Florine Seidel & Amanda J. Kiliaan

  3. Department of Bariatric Surgery, Vitalys, Rijnstate Hospital, Arnhem, the Netherlands

    Debby Vreeken & Eric J. Hazebroek

  4. Department for Metabolic Health Research, The Netherlands Organization for Applied Scientific Research TNO, Leiden, The Netherlands

    Florine Seidel & Robert Kleemann

  5. Division Human Nutrition and Health, Wageningen University, Wageningen, the Netherlands

    Rinke Stienstra & Eric J. Hazebroek

  6. Department of Computational Biology for Individualized Medicine, Centre for Individualized Infection Medicine & TWINCORE, Joint ventures between the Helmholtz-Centre for Infection Research and the Hannover Medical School, Hannover, Germany

    Yang Li

  7. Department of Medical Genetics, “Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania

    Leo A. B. Joosten

  8. Department of Immunology and Metabolism, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany

    Mihai G. Netea

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Contributions

Julia van Tuijl: Data curation, Formal analysis, Investigation, Methodology, Visualisation, Writing – original draft. Debby Vreeken: Formal analysis, Investigation, Methodology, Visualisation, Writing – original draft. Wieteke Broeders: Investigation, Writing – original draft. Benjamin Cossins: Data curation, Formal analysis, Methodology, Visualisation, Writing – review and editing. Liesbeth van Emst: Formal analysis, Methodology, Writing – review and editing. Florine Seidel: Formal analysis, Methodology, Writing – review and editing. Rinke Stienstra: Methodology, Supervision, Writing – review and editing. Yang Li: Formal analysis, Methodology, Supervision, Writing – review and editing. Leo A. B. Joosten: Supervision, Writing – review and editing. Mihai G. Netea: Supervision, Writing – review and editing. Eric J. Hazebroek: Conceptualisation, Funding acquisition, Resources, Supervision, Writing – review and editing. Robert Kleemann: Resources, Supervision, Writing – review and editing. Amanda J. Kiliaan: Conceptualization, Funding acquisition, Supervision, Writing – review and editing. Siroon Bekkering: Conceptualization, Formal analysis, Visualisation, Supervision, Writing – review and editing. Niels P. Riksen: Conceptualization, Funding acquisition, project administration, supervision, Writing – review and editing.

Corresponding author

Correspondence to Niels P. Riksen.

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Competing interests

LABJ is scientific founder of TTxD and Lemba TX. MGN is scientific founder of TTxD, Lemba and Biotrip.

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van Tuijl, J., Vreeken, D., Broeders, W. et al. The long-term effect of metabolic bariatric surgery on innate immune cell phenotype and function. Int J Obes 49, 2473–2483 (2025). https://doi.org/10.1038/s41366-025-01886-3

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