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2015 ; 2
(ä): 1
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Altered NK cell function in obese healthy humans
#MMPMID26217516
Laue T
; Wrann CD
; Hoffmann-Castendiek B
; Pietsch D
; Hübner L
; Kielstein H
BMC Obes
2015[]; 2
(ä): 1
PMID26217516
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BACKGROUND: Obesity is associated with an elevated risk for several types of
cancer and thus a major health hazard. However, the mechanism between overweight
and cancer susceptibility is still elusive. Leptin, mainly produced by adipocytes
links food intake and energy expenditure. In addition, recent studies have shown
an immunomodulatory impact of leptin on NK cells. The purpose of the present
study was to investigate whether leptin stimulation of NK cells from obese humans
leads to altered functions as compared to NK cells from lean subjects. On the
basis of body mass index 20 healthy individuals were classified in two groups:
normal weight (<25 kg/m(2)) and obese (>30 kg/m(2)). Peripheral blood mononuclear
cells (PBMC) were isolated from blood samples. We used flow cytometry to assess
differences in phenotype and activity markers (CD107a, CD178 and TRAIL) of PBMCs
between both groups. Furthermore, we determined after short-term in vitro leptin
stimulation the phosphorylation of JAK2, downstream target of the intracellular
signaling cascade of the leptin receptor, by Western Blotting and numbers of
NK-cell-tumor-cell-conjugates as well as Granzyme(+) and IFN-?(+) NK cells by
flow cytometry. Finally, the proliferative capacity of control and long-term
(7 days) leptin-stimulated NK cells was examined. RESULTS: As opposed to similar
NK cell counts, the number of CD3(+)CD56(+) cells was significantly lower in
obese compared to lean subjects. Human NK cells express the leptin receptor
(Ob-R). For further determination of Ob-R, intracellular target proteins of PBMCs
were investigated by Western Blotting. Phosphorylation of JAK2 was lower in obese
as compared to normal weight subjects. Furthermore, significantly lower levels of
TNF-related apoptosis-inducing ligand (TRAIL) as an NK cell functional marker in
obese subjects were found. In vitro leptin stimulation resulted in a higher
production of interferon-? in NK cells of normal weight subjects. Interestingly,
long-term leptin stimulation had no significant influence on numbers of
proliferating NK cells. CONCLUSIONS: NK cells from obese healthy humans show
functional deficits and altered responses after in vitro leptin challenge.
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