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  • Original Article
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Animal Models

CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice

International Journal of Obesity volume 39, pages 977–985 (2015)Cite this article

Subjects

Abstract

Background/objectives:

Lymphocytes have a critical role in visceral adipose tissue (AT) inflammation. The CD28 costimulatory molecule is required for lymphocyte activation and for the development of a functional regulatory T cells (Tregs) compartment; however, its role during obesity is unknown.

Methods:

During diet-induced obesity, we investigated the effects of selective interference with CD28 signaling using knockout mice (Cd28KO) and a CTLA4-Ig fusion protein inhibiting CD28-B7 interactions.

Results:

Cd28 deficiency decreased pathogenic T cells and Treg content within AT without changing the macrophages number. Cd28KO epididymal but not subcutaneous fat was characterized by enlarged adipocytes, reduced levels of inflammatory cytokines and increased Glut4, adiponectin and lipogenic enzyme mRNA levels. This was associated with reduced inflammation, fat accumulation and enhanced glucose metabolism in liver. Weight gain and fasting glucose tolerance were not affected. CTLA4-Ig injections reduced the number of T cells in epididymal AT (epiAT) but not the inflammatory cytokines levels and failed to improve liver fat accumulation.

Conclusions:

Deletion of CD28 creates a new pro/anti-inflammatory balance in epiAT and liver and exerts a protective effect against hepatic steatosis.

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Acknowledgements

We thank V Ferrier-Depraetere (Institut Paoli-Calmettes) for thoughtful reading of the manuscript. We are grateful to P Guichard and P Gibier for their help in animal handling feeding and body weight monitoring; F Gianardi (inter-IFR animal facility) for taking care of the Cd28KO mouse colony and finally C Fossat, I Arnoux and the CRCM cytometry platform for FACS analysis. This work was supported by the “Societé Francophone du Diabète”, the European society of cardiology (grant to MP) and by the “Comité du Var de la Ligue contre le cancer” (to JAN). JA Nunès and D Olive laboratory is supported by the Fondation pour la Recherche Médicale (Equipe FRM DEQ20140329534). SO Morin is supported by a fellowship from Aix-Marseille Université. D Olive is a scholar of the Institut Universitaire de France.

Author information

Author notes

  1. F Peiretti and J A Nunès: These authors contributed equally to this work

Authors and Affiliations

  1. Inserm, U1062, Marseilles, France

    M Poggi, D Bastelica, R Govers, M Canault, D Bernot, O Georgelin, M Verdier, M-C Alessi & F Peiretti

  2. Inra, UMR1260, Marseilles, France

    M Poggi, D Bastelica, R Govers, M Canault, D Bernot, O Georgelin, M Verdier, M-C Alessi & F Peiretti

  3. Aix-Marseille Université, NORT, Marseilles, France

    M Poggi, D Bastelica, R Govers, M Canault, D Bernot, O Georgelin, M Verdier, M-C Alessi & F Peiretti

  4. Inserm, U1068, CRCM, Marseilles, France

    S O Morin, D Olive & J A Nunès

  5. Institut Paoli-Calmettes, Marseilles, France

    S O Morin, D Olive & J A Nunès

  6. Aix-Marseille Université, UM 105, Marseilles, France

    S O Morin, D Olive & J A Nunès

  7. CNRS, UMR7258, CRCM, Marseilles, France

    S O Morin, D Olive & J A Nunès

  8. Inserm, U1048, Toulouse, France

    R Burcelin

  9. Université Paul Sabatier, I2MC, Toulouse, Cedex 4, France

    R Burcelin

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  1. M Poggi
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Corresponding author

Correspondence to M Poggi.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Poggi, M., Morin, S., Bastelica, D. et al. CD28 deletion improves obesity-induced liver steatosis but increases adiposity in mice. Int J Obes 39, 977–985 (2015). https://doi.org/10.1038/ijo.2015.26

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  • DOI: https://doi.org/10.1038/ijo.2015.26

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