Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

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

International Journal of Obesity volume 24, pages 1212–1216 (2000)Cite this article

Abstract

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 erythropoietin. The concentration of leptin required for this effect was rather high but within the range of plasma leptin levels observed in obesity. Two results further support the hypothesis that leptin may be involved in the leukocytosis associated with obesity: (i) leptin concentrations in bone marrow and plasma of subjects studied were highly correlated; (ii) leptin and leukocyte count were correlated only in obese subjects. Paracrine effects of locally released leptin from bone marrow adipocytes could also be involved in the regulation of hemopoiesis, a hypothesis supported by marrow immunocytochemistry revealing the close association of CD34+ cells with adipocytes and by previous demonstration that leptin is secreted at a high level by these cells.

CONCLUSION: These results indicate that leptin acts on human multilineage CD34+ cells and that high plasma leptin levels associated with obesity could participate in the differentiation of granulocytes from hemopoietic progenitors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Tritos NA, Mantzoros CS . Leptin: its role in obesity and beyond Diabetologia 1997 40: 1371–1379.

    Article  CAS  PubMed  Google Scholar 

  2. Campfield LA, Smith FJ . Overview: neurobiology of OB protein (leptin) Proc Nutr Soc 1998 57: 429–440.

    Article  CAS  PubMed  Google Scholar 

  3. Flier JS . What's in a name? In search of leptin's physiologic role J Clin Endocrinol Metab 1998 83: 1407–1413.

    CAS  PubMed  Google Scholar 

  4. Gainsford T, Willson TA, Metcalf D, Handman E, McFarlane C, Ng A, Nicola NA, Alexander WS, Hilton DJ . Leptin can induce proliferation, differentiation, and functional activation of hemopoietic cells Proc Natl Acad Sci USA 1996 93: 14564–14568.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bennett BD, Solar GP, Yuan JQ, Mathias J, Thomas GR, Matthews W . A role for leptin and its cognate receptor in hematopoiesis Curr Biol 1996 6: 1170–1180.

    Article  CAS  PubMed  Google Scholar 

  6. Cioffi J, Shafer A, Zupancic T, Smithbur J, Mikhail A, Platika D, Snodgrass H . Novel B219/OB receptor isoforms: possible role of leptin in hematopoiesis and reproduction Nature Med 1996 2: 585–589.

    Article  CAS  PubMed  Google Scholar 

  7. Pratley RE, Wilson C, Bogardus C . Relation of the white blood cell count to obesity and insulin resistance: effect of race and gender Obes Res 1995 3: 563–571.

    Article  CAS  PubMed  Google Scholar 

  8. Nanji AA, Freeman JB . Relationship between body weight and total leukocyte count in morbid obesity Am J Clin Pathol 1985 84: 346–347.

    Article  CAS  PubMed  Google Scholar 

  9. Wilson CA, Bekele G, Nicolson M, Ravussin E, Pratley RE . Relationship of the white blood cell count to body fat: role of leptin Br J Haematol 1997 99: 447–451.

    Article  CAS  PubMed  Google Scholar 

  10. Hirose H, Saito I, Kawai T, Nakamura K, Maruyama H, Saruta T . Serum leptin level: possible association with haematopoiesis in adolescents, independent of body mass index and serum insulin Clin Sci 1998 94: 633–636.

    Article  CAS  Google Scholar 

  11. de Winter EA, Coutinho LH, Pei X, Marsh JCW, Hows J, Luft T, Testa NG . Comparison of purity and enrichment of CD34+ cells from bone marrow, umbilical cord and peripheral blood (primed for apheresis) using five separation systems Stem Cells 1995 13: 524–532.

    Article  Google Scholar 

  12. Allegraud A, Dobo I, Praloran V . Collagen gel culture of the human hematopoietic progenitors CFU-GM, CFU-E, and BFU-E Meth Mol Biol 1997 75: 221–230.

    CAS  Google Scholar 

  13. Delsol G, Blancher A, al Saati T, Ralfkiaer E, Lauritzen A, Bruigeres L, Brousset P, Rigal-Huguet F, Mazerolles C, Robert A . Antibody BNH9 detects red blood cell-related antigens on anaplastic large cell (CD30+) lymphomas Br J Cancer 1991 64: 321–326.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Laharrague P, Larrouy D, Fontanilles A-M, Truel N, Campfield A, Tenenbaum R, Galitztky J, Corberand JX, Pénicaud L, Casteilla L . High expression of leptin by human bone marrow adipocytes in primary culture FASEB J 1998 12: 747–752.

    Article  CAS  PubMed  Google Scholar 

  15. Rosenbaum M, Nicholson M, Hirsch J, Heymsfield SB, Gallagher D, Chu F, Leibel RL . Effects of gender, body composition, and menopause on plasma concentrations of leptin J Clin Endocrinol Metab 1996 81: 3424–3427.

    CAS  PubMed  Google Scholar 

  16. Saad MF, Damani S, Gingerich RL, Riad-Gabriel MG, Khan A, Boyadjian R, Jinagouda SD, El-Tawil K, Rude RK, Kamdar V . Sexual dimorphism in plasma leptin concentration J Clin Endocrinol Metab 1997 82: 579–584.

    CAS  PubMed  Google Scholar 

  17. Umemoto Y, Tsuji K, Yang FC, Ebihara Y, Kaneko A, Furukawa S, Nakahata T . Leptin stimulates the proliferation of murine myelocytic and primitive hematopoietic progenitor cells Blood 1997 90: 3438–3443.

    CAS  PubMed  Google Scholar 

  18. Mikhail AA, Beck EX, Shafer A, Barut B, Smith Gbur J, Zupancic TJ, Schweitzer AC, Cioffi JA, Lacaud G, Ouyang B, Keller G, Snodgrass HR . Leptin stimulates fetal and adult erythroid and myeloid development Blood 1997 89: 1507–1512.

    CAS  PubMed  Google Scholar 

  19. Lee F-YJ, Li Y, Yang EK, Yang SQ, Lin HZ, Trush MA, Dannenberg AJ, Diehl AM . Phenotypic abnormalities in macrophages from leptin-deficient, obese mice Am J Physiol 1999 276: C386–C394.

    Article  CAS  PubMed  Google Scholar 

  20. Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, Diehl AM . Leptin regulates proinflammatory immune responses FASEB J 1998 12: 57–65.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are grateful to RI Tenenbaum for her assistance in leptin assays and to N Crowte for preparation of the manuscript.

Author information

Authors and Affiliations

  1. UPRESA CNRS 5018, IFR31, UPS, Hôpital Toulouse Rangueil, France

    P Laharrague, A-M Fontanilles, JX Corberand, L Pénicaud & L Casteilla

  2. Service de Médecine et Nutrition, Hôtel-Dieu Paris, France

    J-M Oppert & B Guy-Grand

  3. Département d'Anatomie Pathologique, Hôpital Toulouse Purpan, France

    P Brousset

  4. Département d'Epidémiologie, Hôtel-Dieu Toulouse, France

    J-P Charlet

  5. Hoffmann-La Roche, Nutley, New Jersey, USA

    A Campfield

Authors
  1. P Laharrague
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J-M Oppert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P Brousset
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J-P Charlet
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Campfield
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A-M Fontanilles
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. B Guy-Grand
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. JX Corberand
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. L Pénicaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L Casteilla
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P Laharrague.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Laharrague, P., Oppert, JM., Brousset, P. et al. High concentration of leptin stimulates myeloid differentiation from human bone marrow CD34+ progenitors: potential involvement in leukocytosis of obese subjects. Int J Obes 24, 1212–1216 (2000). https://doi.org/10.1038/sj.ijo.0801377

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801377

Keywords

This article is cited by

Search

Advanced search

Quick links