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Blood, Vol. 93 No. 12 (June 15), 1999: pp. 4444-4445

CORRESPONDENCE

Relationship Between Levels of Leptin and Hemoglobin in Japanese Men


    LETTER

To the Editor:

Leptin, the ob gene product secreted by adipocyte, decreases food intake while it increases energy expenditure and functions as an important signal for the regulation of body weight.1-3 The leptin receptor is an isoform of the B219 gene product, a member of the hematopoietin receptor family, which is expressed in very primitive hematopoietic cells.4 Recent studies showed that leptin plus erythropoietin acted synergistically to increase erythroid development in vitro.5,6 These findings led us to examine the relationship between the serum levels of leptin and hemoglobin.

We surveyed 708 male workers who were not taking any medication. Information regarding smoking habits, alcohol consumption, and physical activity was obtained by questionnaire and/or from medical records. As for the question regarding physical activity, subjects were asked to choose one from the following four answers: no exercise at all, once or twice per month, once or twice per week, and three times or more per week. Blood was drawn in the morning after a 12-hour or longer fast. Serum leptin and insulin were determined by radio immunoassay (Linco Research Inc, St Charles, MO) and enzyme immunoassay (Dinabot, Tokyo, Japan), respectively.

When the subjects were divided into three groups according to their hemoglobin level (<14.5 g/dL [the lowest quintile], 14.5 to 15.8 g/dL, and >= 15.8 g/dL [the highest quintile]), a negative correlation was observed between the levels of leptin and those of hemoglobin, after being adjusted for age, body-mass index, and physical activity (Table 1). The negative correlation became more apparent after further adjustment for the insulin level. In contrast, when similar analysis was performed to examine the relationship between the levels of leptin and white blood cell counts, no correlation was observed between these two variables after being adjusted for related variables.

                              
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Table 1. Relationship Between Levels of Leptin and Hemoglobin in Male Workers

This is the first epidemiologic study showing an association between the levels of leptin and those of hemoglobin. Wilson et al7 failed to show such a correlation between leptin and red blood cell count without adjusting for leptin-related variables. The gender-dependent difference in serum leptin may be due to the difference of hemoglobin levels, adding to fat mass and sex hormones.8

Erythropoiesis is thought to be regulated by erythropoietin, which, in adults, is produced mainly in kidneys, in response to hypoxia.9 Leptin production occurs mainly in adipocytes, but there has been no report showing that adipocytes have a sensor for hypoxia. It is interesting that bone marrow contains many adipocytes, the role of which is not clear.

Although the effect of leptin on hematopoiesis may be modest, the results of our epidemiologic study, together with those of previous studies performed in vitro,5,6 suggest that leptin may play some role in hematopoiesis in humans. Further cross-sectional and prospective studies are needed to elucidate the relationship between leptin and hematopoiesis.

Masako Togo
Kazuhisa Tsukamoto
Hiroaki Satoh
Masumi Hara
Department of Metabolism
Internal Medicine

Azusa Futamura
Hideo Nakarai
Kazuhiko Nakahara
Yoshiaki Hashimoto
Department of Clinical Laboratory Medicine
Graduate School of Medicine
The University of Tokyo
Tokyo, Japan


    REFERENCES

1. Frederich RC, Hamann A, Anderson S, Lollmann B, Lowell BB, Flier JS: Leptin levels reflect body lipid content in mice: Evidence for diet-induced resistance to leptin action. Nat Med 1:1311, 1995[Medline] [Order article via Infotrieve]

2. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F: Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269:540, 1995[Abstract/Free Full Text]

3. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JM: Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543, 1995[Abstract/Free Full Text]

4. Cioffi JA, Shafer AW, Zupancic TJ, Smith-Gbur J, Mikhail A, Platika D, Snodgrass HR: Novel B219/OB receptor isoforms: Possible role of leptin in hematopoiesis and reproduction. Nat Med 2:585, 1996[Medline] [Order article via Infotrieve]

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 6:1170, 1996[Medline] [Order article via Infotrieve]

6. Mikhail AA, Beck EX, Shafer A, Barut B, Gbur JS, Zupancic TJ, Schweitzer AC, Cioffi JA, Lacaud G, Ouyang B, Keller G, Snodgrass HR: Leptin stimulates fetal and adult erythroid and myeloid development. Blood 89:1507, 1997[Abstract/Free Full Text]

7. 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 99:447, 1997[Medline] [Order article via Infotrieve]

8. Roemmich JN, Clark PA, Berr SS, Mai V, Mantzoros CS, Flier JS, Weltman A, Rogol AD: Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids. Am J Physiol 275:E543, 1998[Abstract/Free Full Text]

9. Wang GL, Semenza GL: Molecular basis of hypoxia-induced erythropoietin expression. Curr Opin Hematol 3:156, 1996[Medline] [Order article via Infotrieve]
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