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The role of leptin in the immune system has been well established. While adipocytes represent the major source, leptin production by lymphocytes, infiltrating at the site of inflammation, was recently demonstrated. However, the significance of this locally released leptin remains unresolved. In the present study, two models in which absence of leptin-signalling is associated with protection were employed: the model of ConA-induced hepatitis and the CD4+CD45Rbhigh transfer model of colitis. For the ConA model, scid mice were reconstituted with either WT or leptin-deficient ( ob/ob) CD4+ T cells. Eight weeks post transfer, ConA was injected and serum ALT, TNFα, leptin as well as liver mononuclear cell activation and histological signs of inflammation were evaluated. No difference between recipients of WT or ob/ob cells was observed for any of the parameters evaluated. In the second model, either WT or ob/ob CD4+CD45Rbhigh cells were transferred into scid mice. No histological differences were detected, although recipients of ob/ob cells showed higher weight loss compared to recipients of WT cells. Spontaneous production of IL-6 from colon cultures obtained from recipients of ob/ob cells was reduced compared to recipients of WT cells, whereas stimulation of lamina propria lymphocytes with leptin resulted in a higher IFNγ release in recipients of ob/ob cells compared to recipients of WT cells. In conclusion, the present study provides evidence that T cell-derived leptin does not play a major role in the regulation of the inflammatory process, indicating that the adipose tissue is the critical player in the immune-modulating effects of leptin. [ABSTRACT FROM AUTHOR]

Background: Leptin regulates appetite through the long isoform of its receptor in the hypothalamus. Although leptin regulates immune responses, it is still unknown whether a direct effect of leptin on lymphocytes is required. Aims: To clarify whether expression of leptin receptors on I lymphocytes modulates intestinal inflammation in mice. Methods: The model of colitis induced by transfer of CD4+CD45RBhigh (RBhigh) cells into scid mice was used. Wild-type (WT) or leptin receptor deficient (db/db) RBhigh cells were transferred into scid mice and development of colitis evaluated. Results: Leptin receptors were expressed on both RBhigh and RBhigh cells. Intestinal lymphocytes of mice with colitis expressed high leptin levels compared with healthy controls whereas the opposite was true for serum leptin levels. Transfer of RBhigh cells from db/db mice induced delayed disease compared with transfer of WT cells. A high rate of apoptosis in lamina propria lymphocytes and reduced cytokine production were observed early on in scid mice receiving db/db RBhigh cells. These effects were not due to the high levels of glucocorticoids present in db/db mice as administration of corticosterone to WT mice failed to reproduce this phenomenon. High expression of peroxisome proliferator activated receptor γ was observed in the colon of recipients of db/db compared with WT cells. Freshly isolated db/db RBhigh cells produced low levels of interferon γ. Despite delayed onset of colitis, as disease progressed differences between mice receiving WT or db/db cells were no longer apparent. Conclusions: These results suggest that leptin affects the immune response, partly by acting on the long isoform of its receptor expressed on T lymphocytes. [ABSTRACT FROM AUTHOR]