Interrelationship between lymphocytes and leptin i

Authors: Karine Lolmède Alexia ZakaroffGirard Cedric Dray MarieLaure Renoud Danièle Daviaud Rémy Burcelin Max Lafontan Jean Galitzky Anne Bouloumié

Publish Date: 2015/02/12

Volume: 71, Issue: 3, Pages: 497-507

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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 dietinduced obesity the status of immune cells in subcutaneous and epididymal fat depots in wildtype and immunodeficient Rag2−/− mice submitted to nutritional challenge ie 48h fasting and 1week 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 wildtype 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 Oneweek refeeding was sufficient to reverse the fastinginduced 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 fastedinduced upregulation of FGF21 expression was maintained as well as the lipolytic responses The present results demonstrate that in a context of dietinduced obesity fastinginduced immunosuppression is restricted to fat depots in immunocompetent mice Lack of adipocyte leptin regulation and fastinginduced 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 statusThis 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 GirmaVidal for the excellent assistance for adipocyte RNA extraction and realtime PCR experiments

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