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Interrelationship between lymphocytes and leptin in fat depots of obese mice revealed by changes in nutritional status

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Abstract

The mechanisms underlying the relationships between nutritional status and immunity remain to be fully characterized. The present study was undertaken to analyze by flow cytometry, in the context of diet-induced obesity, the status of immune cells in subcutaneous, and epididymal fat depots in wild-type and immunodeficient Rag2−/− mice submitted to nutritional challenge, i.e., 48-h fasting and 1-week refeeding. In parallel, the responsiveness of mature adipocytes and immune cells in bone marrow, lymph node, and liver were also analyzed. The results show that fasting in obese wild-type mice induces a prominent lipolysis in epididymal AT and immunosuppression restricted to both subcutaneous and epididymal AT, characterized by reduced number of CD4+ T and B lymphocytes and M1/M2 macrophages associated with reduced leptin and increased FGF21 expression in mature adipocytes. One-week refeeding was sufficient to reverse the fasting-induced effects. Obese immunodeficient mice under nutritional challenge exhibited no changes in adipocyte leptin expression and no marked trafficking of AT macrophages or NK cells, while the fasted-induced upregulation of FGF21 expression was maintained as well as the lipolytic responses. The present results demonstrate that, in a context of diet-induced obesity, fasting-induced immunosuppression is restricted to fat depots in immunocompetent mice. Lack of adipocyte leptin regulation and fasting-induced immunosuppression in obese immunodeficient mice strongly suggests that lymphocytes are involved in the modulation of adipocyte leptin expression on one hand and on the other that leptin is involved in the immune changes in AT according to nutritional status.

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Acknowledgments

This work was supported by grants from the Agence Nationale de la Recherche (ANR, Transflora). The authors gratefully thank the GenoToul Animal Care Facility of Rangueil Hospital (UMS US006/Inserm) and M. Girma-Vidal for the excellent assistance for adipocyte RNA extraction and real-time PCR experiments.

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Authors and Affiliations

  1. Inserm, UMR1048, Team 1, Institute of Metabolic and Cardiovascular Diseases, BP84225, 31432, Toulouse Cedex 4, France

    Karine Lolmède, Alexia Zakaroff-Girard, Marie-Laure Renoud, Max Lafontan, Jean Galitzky & Anne Bouloumié

  2. Paul Sabatier University, 118, Route de Narbonne, 31062, Toulouse Cedex 9, France

    Karine Lolmède, Alexia Zakaroff-Girard, Cedric Dray, Marie-Laure Renoud, Danièle Daviaud, Rémy Burcelin, Max Lafontan, Jean Galitzky & Anne Bouloumié

  3. Inserm, UMR1048, Team 3, Institute of Metabolic and Cardiovascular Diseases, BP84225, 31432, Toulouse Cedex 4, France

    Cedric Dray & Danièle Daviaud

  4. Inserm, UMR1048, Team 2, Institute of Metabolic and Cardiovascular Diseases, BP84225, 31432, Toulouse Cedex 4, France

    Rémy Burcelin

Authors
  1. Karine Lolmède
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  2. Alexia Zakaroff-Girard
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  3. Cedric Dray
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  4. Marie-Laure Renoud
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  6. Rémy Burcelin
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  7. Max Lafontan
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  8. Jean Galitzky
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  9. Anne Bouloumié
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Correspondence to Alexia Zakaroff-Girard.

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Lolmède, K., Zakaroff-Girard, A., Dray, C. et al. Interrelationship between lymphocytes and leptin in fat depots of obese mice revealed by changes in nutritional status. J Physiol Biochem 71, 497–507 (2015). https://doi.org/10.1007/s13105-015-0388-x

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  • DOI: https://doi.org/10.1007/s13105-015-0388-x

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