Leptin acts not only as an anorexigenic hormone but is also involved in the regulation of cell-mediated immunity. However, since the impact of leptin on NK cells is currently elusive, we investigated the body weight-dependent leptin effects on NK cells numbers and function.
In a first set of experiments leptin and MADB106 tumor cells were injected intravenously in male lean and diet-induced obese Lewis and F344 rats. In a second set of experiments an in vivo NK cell depletion with consecutive cross-over re-transfusion of NK cells in F344 rats was performed. Blood NK cell numbers were determined in blood and spleen by FACS and immunohistochemistry and the activity of NK cells was measured by chromium release assay. The Ob-R expression on NK cells was analyzed by confocal laser scanning and qRT-PCR. Intracellular signaling cascades downstream of Ob-R were evaluated by western blotting. Leptin application resulted in increased NK cell cytoxicity in lean rats but failed to activate NK cells from obese rats. We found Ob-R to be expressed on NK cells and qRT-PCR showed significantly higher Ob-Rb mRNA levels in NK cells from obese rats compared to lean littermates. In contrast, post receptor signaling was altered in obese animals with significantly lower activation of post-receptor signaling components (JAK-2p, PKBpT308, AMPKα-pT172) upon the leptin challenge. Results of the cross-over transfusion of NK cells impressively showed a time-dependent host-specific distribution and activation of NK cells.
The results for the first time demonstrate milieu-specific altered NK cell functions in obese animals and the reversibility of these changes after transfusion in normal weight littermates. The data have important implications for the influence of weight gain and loss on immune cell numbers and functions.
03 - 07 May 2008
European Society of Endocrinology