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Physiology and Biochemistry

Role of IL-18 in adipose tissue remodeling and metabolic dysfunction

International Journal of Obesity (2024)Cite this article

Subjects

Abstract

Background/objectives

Proinflammatory cytokines are increased in obese adipose tissue, including inflammasome key masters. Conversely, IL-18 protects against obesity and metabolic dysfunction. We focused on the IL-18 effect in controlling adipose tissue remodeling and metabolism.

Materials/subjects and methods

We used C57BL/6 wild-type (WT) and interleukine-18 deficient (IL-18−/−) male mice fed a chow diet and samples from bariatric surgery patients.

Results

IL-18−/− mice showed increased adiposity and proinflammatory cytokine levels in adipose tissue, leading to glucose intolerance. IL-18 was widely secreted by stromal vascular fraction but not adipocytes from mice’s fatty tissue. Chimeric model experiments indicated that IL-18 controls adipose tissue expansion through its presence in tissues other than bone marrow. However, IL-18 maintains glucose homeostasis when present in bone marrow cells. In humans with obesity, IL-18 expression in omental tissue was not correlated with BMI or body fat mass but negatively correlated with IRS1, GLUT-4, adiponectin, and PPARy expression. Also, the IL-18RAP receptor was negatively correlated with IL-18 expression.

Conclusions

IL-18 signaling may control adipose tissue expansion and glucose metabolism, as its absence leads to spontaneous obesity and glucose intolerance in mice. We suggest that resistance to IL-18 signaling may be linked with worse glucose metabolism in humans with obesity.

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Fig. 1: Effect of IL-18 lack on mice’s body composition and glucose metabolism.
Fig. 2: Cytokine levels in IL-18 deficient mice.
Fig. 3: Mesenchymal stem cells in IL-18 deficient mice.
Fig. 4: IL-18 expression and secretion of mouse white adipose tissue.
Fig. 5: Adiposity, glucose metabolism and inflammatory alterations in the chimera groups.
Fig. 6: Correlation between IL-18 and its receptors gene expression and bioclinical parameters in omental adipose tissue of subjects with severe obesity.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Comité français d’Evaluation de la Coopération Universitaire et Scientifique avec le Brésil (COFECUB) grants no 88887.130206/2017-01 and 88887.879203/2023-01. We thank Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG), Pró-Reitoria de Pesquisa (PRPq) from UFMG, National Council for Scientific and Technological Development (CNPq/Brazil) by financial support, and National Agency of Research (e.g., Captor program) and the French Foundation for Medical Research, FRM. The clinical investigation was performed at the Human Nutrition Research Center (CRNH Ile de France), Pitié-Salpêtrière Hospital. We also thank Florence Marchelli, APHP, for data management and Professor Leda Vieira for providing the IL-18 knockout mice.

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Author notes

  1. These authors contributed equally: Jaqueline Pereira Lana, Marina Chaves de Oliveira.

Authors and Affiliations

  1. Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Jaqueline Pereira Lana, Marina Chaves de Oliveira, Ana Letícia Malheiros Silveira, Kátia Anunciação Costa & Adaliene Versiani Matos Ferreira

  2. Faculty of Nutrition, Universidade Federal de Alfenas, Alfenas, Brazil

    Letícia Tamie Paiva Yamada

  3. Department of Cellular Biology, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil

    Simone Vargas da Silva & Agatha de Assis-Ferreira

  4. Sorbonne Université, INSERM, UMRS 1166, F-75013, Paris, France

    Emmanuel L. Gautier & Sébastien Dussaud

  5. Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Vanessa Pinho

  6. Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil

    Mauro Martins Teixeira

  7. Sorbonne Université, Inserm, Nutrition and Obesities: Systemic Approaches, Nutriomics, Research Unit, F-75013, Paris, France

    Geneviève Marcelin & Karine Clément

  8. Assistance Publique Hôpitaux de Paris, APHP, Nutrition Department, Pitié-Salpêtrière Hospital, F-75013, Paris, France

    Geneviève Marcelin & Karine Clément

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Contributions

JPL, MCO, GM, and AVMF: conceptualization and study design; JPL, MCO, ALMS, LTPY, KAC, AAF, and SD: Investigation; SVS, ELG, VP, MMT, GM, KC, AVMF: funding acquisition and resources; JPL, MCO, ALMS, SVS, ELG, GM, KC, and AVMF: writing—original draft, review & editing.

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Correspondence to Adaliene Versiani Matos Ferreira.

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Lana, J.P., de Oliveira, M.C., Silveira, A.L.M. et al. Role of IL-18 in adipose tissue remodeling and metabolic dysfunction. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01507-5

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