title: Interrelationship between lymphocytes and leptin in fat depots of obese mice revealed by changes in nutritional status.
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.
authors: Inserm, UMR1048, Team 1, Institute of Metabolic and Cardiovascular Diseases, BP84225, 31432, Toulouse Cedex 4, France.
authors: Karine
authors: K
authors: Lolmède
authors: Alexia
authors: A
authors: Zakaroff-Girard
authors: Cedric
authors: C
authors: Dray
authors: Marie-Laure
authors: ML
authors: Renoud
authors: Danièle
authors: D
authors: Daviaud
authors: Rémy
authors: R
authors: Burcelin
authors: Max
authors: M
authors: Lafontan
authors: Jean
authors: J
authors: Galitzky
authors: Anne
authors: A
authors: Bouloumié
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects; D007108:Immune Tolerance; D020738:Leptin / Q000502:physiology*; D008099:Liver / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; D020738:Leptin; C499308:Rag2 protein, mouse