High concentration of leptin stimulates myeloid differentiation from humanbone marrow CD34+progenitors: potential involvement in leukocytosis of obese subjects

OBJECTIVE AND DESIGN: As well as its involvement in control of adipose mass and body energy balance, several reports suggest a link between leptin and hemopoiesis. To test its putative role in human hemopoiesis, we developed a homologous system, ie recombinant human leptin treatment of purified CD34 + progenitors from adult human bone marrow. RESULTS: Leptin (50 - 100 ng/ml) significantly stimulated the appearance of granulocyte-macrophage colonies in the presence or absence of erythropoiet in. The concentration of leptin required for this effect was rather high bu t within the range of plasma leptin levels observed in obesity. Two results further support the hypothesis that leptin may be involved in the leukocyt osis associated with obesity: (i) leptin concentrations in bone marrow and plasma of subjects studied were highly correlated; iii) leptin and leukocyt e count were correlated only in obese subjects. Paracrine effects of locall y released leptin from bone marrow adipocytes could also be involved in the regulation of hemopoiesis, a hypothesis supported by marrow immunocytochem istry revealing the close association of CD34+ cells with adipocytes and by previous demonstration that leptin is secreted at a high level by these ce lls. CONCLUSION: These results indicate that leptin acts on human multilineage C D34+ cells and that high plasma leptin levels associated with obesity could participate in the differentiation of granulocytes from hemopoietic progen itors.