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.

Table 1.

Relationship Between Levels of Leptin and Hemoglobin in Male Workers

Hemoglobin (g/dL)
<14.514.5-15.8 ≧14.9
n  148  422  138  
Age (yr) 47.7 (0.5)  45.9 (0.3)* 44.6 (0.6) 
Body-mass index (kg/m2)  22.30 (0.2)  23.2 (0.1) 24.1 (0.2) 
Exercise (times/mon)  2.8 (0.3) 2.5 (0.1)  1.8 (0.2)* 
Cigarettes (pieces/d) 13.0 (1.3)  12.6 (0.7)  14.9 (1.4)  
Alcohol (mL/wk) 202.0 (15.0)  197.0 (8.3)  203.0 (15.6)  
Leptin (ng/mL) 3.37 (0.14)  3.61 (0.09)  3.68 (1.58)  
Insulin (μU/mL)  3.93 (0.17)  4.56 (2.24)* 5.40 (0.31) 
Adjusted for age, body-mass index, and exercise  
 Leptin (ng/mL)  3.71 (0.12)  3.60 (0.07)  3.34 (0.13) 
 Insulin (μU/mL)  4.33 (0.20)  4.54 (0.11) 5.02 (0.20) 
Adjusted for age, body-mass index, exercise and insulin  
 Leptin (ng/mL)  3.75 (0.12)  3.61 (0.07) 3.27 (0.12)* 
Hemoglobin (g/dL)
<14.514.5-15.8 ≧14.9
n  148  422  138  
Age (yr) 47.7 (0.5)  45.9 (0.3)* 44.6 (0.6) 
Body-mass index (kg/m2)  22.30 (0.2)  23.2 (0.1) 24.1 (0.2) 
Exercise (times/mon)  2.8 (0.3) 2.5 (0.1)  1.8 (0.2)* 
Cigarettes (pieces/d) 13.0 (1.3)  12.6 (0.7)  14.9 (1.4)  
Alcohol (mL/wk) 202.0 (15.0)  197.0 (8.3)  203.0 (15.6)  
Leptin (ng/mL) 3.37 (0.14)  3.61 (0.09)  3.68 (1.58)  
Insulin (μU/mL)  3.93 (0.17)  4.56 (2.24)* 5.40 (0.31) 
Adjusted for age, body-mass index, and exercise  
 Leptin (ng/mL)  3.71 (0.12)  3.60 (0.07)  3.34 (0.13) 
 Insulin (μU/mL)  4.33 (0.20)  4.54 (0.11) 5.02 (0.20) 
Adjusted for age, body-mass index, exercise and insulin  
 Leptin (ng/mL)  3.75 (0.12)  3.61 (0.07) 3.27 (0.12)* 

Values are mean (SE). P values are versus the group with hemoglobin levels of <14.5 g/dL. Statistic analysis was performed using the general linear regression model procedures of Statistical Analysis System (SAS Institute, Cary, NC).

*

P < .01.

P < .001.

P < .05.

This is the first epidemiologic study showing an association between the levels of leptin and those of hemoglobin. Wilson et al7failed 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.

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
1995
1311
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
1995
540
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
1995
543
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
1996
585
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
1996
1170
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
1997
1507
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
1997
447
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
1998
E543
9
Wang
GL
Semenza
GL
Molecular basis of hypoxia-induced erythropoietin expression.
Curr Opin Hematol
3
1996
156
Sign in via your Institution