The white blood cell (WBC) count is correlated to the amount of body f
at in humans, but the mechanism for this association is unknown, Lepti
n, a 16 kD protein produced in adipocytes, circulates in humans in dir
ect proportion to the amount and percentage of body fat. Recent eviden
ce suggests that leptin and the leptin receptor are part of a novel pa
thway which stimulates haemopoiesis. This study was designed to test w
hether fasting plasma leptin concentrations contribute to the relation
ship between the WBC count and body fat. 117 Pima Indians with a wide
range in body composition were studied. The WBC count was positively c
orrelated with percentage of body fat (r = 0.44, P = 0.0001) and fasti
ng plasma leptin concentration (r = 0.38. P = 0.0001). In multiple reg
ression analyses, age, gender and percent body fat were significant in
dependent determinants of the WBC count. After controlling for age and
gender, percent body fat accounted for 23% of the variance in the WBC
count (partial r = 0.48, P = 0.0001). In similar models which also in
cluded plasma leptin concentration, percent body fat remained signific
antly related to the WBC count, but only accounted for 7% of its varia
nce (partial r = 0.27, P = 0.003). Based on these results, and the dem
onstration that leptin directly effects the stimulation of proliferati
on of haemopoietic stem cells in vitro, we hypothesize that the relati
on of the WBC count to percent body fat may be mediated, in part, thro
ugh the effect of leptin.