LEPTIN STIMULATES FETAL AND ADULT ERYTHROID AND MYELOID DEVELOPMENT

The ob gene product, leptin, has been shown in several studies to he i nvolved in weight control and recombinant leptin recently has entered clinical trials to treat obesity. The leptin receptor (OB-R/B219) is e xpressed in a variety of protein isoforms not only in the central nerv ous system, but also in reproductive, and hematopoietic tissues. We re ported recently that the OB-R/B219 was associated with a variety of he matopoietic lineages as well as the small fraction of cells containing the long-term reconstituting hematopoietic stem cells. Herein we repo rt that leptin significantly stimulates the proliferation and differen tiation of yolk sac cells and fetal liver cells and stimulates directl y hematopoietic precursors. Leptin alone can increase the number of ma crophage and granulocyte colonies, and leptin plus erythropoietin act synergistically to increase erythroid development. These data show tha t leptin has a significant, direct effect on early hematopoietic devel opment and can stimulate the differentiation of lineage-restricted pre cursors of the erythrocytic and myelopoietic lineages, These observati ons along with a recent report strongly support our previous hypothesi s that leptin has an unanticipated important role in hematopoietic and immune system development. (C) 1997 by The American Society of Hemato logy.