Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) cells: a novel mechanism of NK cell dysfunction in diet-induced obesity.
Authors
Nave, HeikeMueller, Guenter
Siegmund, Britta
Jacobs, Roland
Stroh, Thorsten
Schueler, Ulrike
Hopfe, Matthias
Behrendt, Patrick
Buchenauer, Tobias
Pabst, Reinhard
Brabant, Georg E
Affiliation
Institute for Functional and Applied Anatomy, Hannover Medical School, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. nave.heike@mh-hannover.deIssue Date
2008-07
Metadata
Show full item recordAbstract
Leptin acts not only as an anorexigenic hormone but also regulates cell-mediated immunity via leptin receptors (Ob-R) expressed on T and B lymphocytes. However, the impact of leptin on natural killer (NK) cells is currently elusive. We evaluated leptin effects on NK cells in relation to the body weight in rats using in vivo and in vitro approaches. Leptin was injected iv in male lean and diet-induced obese Lewis and F344 rats. NK cell numbers were analyzed in blood and spleen by fluorescence activated cell sorting and immunohistochemistry, and the activity of NK cells was measured by chromium release assay. Ob-R expression was investigated by confocal laser scanning and quantitative RT-PCR. To compare leptin-dependent intracellular signaling under basal and leptin- and tumor cell (MADB106)-stimulated conditions, intracellular target proteins of NK cells were evaluated by Western blotting. Number and distribution pattern of splenic NK cells were significantly different in lean and obese animals. Leptin administration resulted in a 4-fold higher stimulation of the NK activity in lean than obese animals. This was not due to a decreased expression of Ob-R because quantitative RT-PCR revealed significantly higher Ob-Rb mRNA levels in NK cells from obese rats. In contrast, postreceptor signaling is differentially abrogated in obese animals with significantly lower activation of postreceptor signaling components (Janus kinase-2p, protein kinase B pT308, AMPalphapT172) after an in vivo leptin challenge. In conclusion, the results for the first time assign leptin a central role as a modulator of NK cell number and activity only in lean but not obese subjects. The differential role of leptin has important implications for the influence of body weight in the response to systemic inflammations and in the immunological defense of cancer.Citation
Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) cells: a novel mechanism of NK cell dysfunction in diet-induced obesity. 2008, 149 (7):3370-8 EndocrinologyJournal
EndocrinologyDOI
10.1210/en.2007-1516PubMed ID
18356278Type
ArticleLanguage
enISSN
0013-7227ae974a485f413a2113503eed53cd6c53
10.1210/en.2007-1516
Scopus Count
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