European Journal of Clinical Nutrition (2001) 55, 244±251
ß 2001 Nature Publishing Group All rights reserved 0954±3007/01 $15.00
www.nature.com/ejcn
Leptin and phospholipid-esteri®ed docosahexaenoic acid
concentrations in plasma of women: observations during
pregnancy and lactation
P Rump1,2*, SJ Otto1,2 and G Hornstra1
1
Nutrition and Toxicology Research Institute, Maastricht (NUTRIM), The Netherlands; and 2Department of Human Biology, Maastricht
University, Maastricht, The Netherlands
Background: The n-3 fatty acid status changes during pregnancy and lactation. Plasma leptin concentrations and
gene expression have been related to n-3 fatty acids.
Objective: To investigate the relation between plasma leptin concentration and the docosahexaenoic acid (22:6n3) content of plasma phospholipids during early pregnancy and the postpartum period.
Design: Leptin (radioimmunoassay) and the phospholipid fatty acid pro®le (capillary gas-liquid chromatography)
were measured in plasma of women during two independent longitudinal observational studies. Dietary intake of
n-3 fatty acids was also determined.
Results: Within the ®rst 10 weeks after the last menstrual period, an almost parallel increase in leptin
concentration and the 22:6n-3 content (mg=l and % wt=wt) of plasma phospholipids was seen (study 1,
n ˆ 21). During the postpartum period (study 2, n ˆ 57), leptin levels decreased quickly, preceding the changes
in 22:6n-3 concentrations. During both studies, leptin concentrations did not consistently relate to dietary intake of
n-3 fatty acids or to 22:6n-3 concentrations in plasma phospholipids. Before and during early pregnancy (study 1),
signi®cant positive associations between leptin levels and the total amount of phospholipid-associated fatty acids
were found. No such association was seen during late pregnancy or the postpartum period (study 2). The
postpartum decrease in leptin levels did not differ between lactating and non-lactating women.
Conclusions: Not the 22:6n-3 content, but the total amount of phospholipid-associated fatty acids was related to
plasma leptin concentration, before and during early pregnancy but not during late pregnancy and the postpartum
period.
Sponsorship: Dutch Organization for Scienti®c Research (NWO, grant no. 904 62 186).
Descriptors: leptin; phospholipids; fatty acids; pregnancy; lactation
European Journal of Clinical Nutrition (2001) 55, 244±251
Introduction
Leptin, 16 kDa product of the `obese-gene' (Zhang et al,
1994), is synthesized in adipose tissue and regarded as a
regulator of energy homeostasis. Serum leptin concentrations are strongly associated to body fatness in adults,
children and infants (Blum et al, 1997; Clapp & Kiess,
1998; Considine et al, 1996; Ellis & Nicolson, 1997;
Marchini et al, 1998). During pregnancy, a marked increase
*Correspondence: P Rump, Department of Human Biology, Maastricht
University, PO Box 616, 6200 MD Maastricht, The Netherlands.
E-mail: [email protected]
Guarantor: P Rump.
Contributors: PR contributed to the design, was responsible for data
analysis and wrote the manuscript. SJO was responsible for study design,
subject recruitment, ®eldwork and assisted in the writing of the
manuscript. GH supervised the project, contributed to study design and
assisted in the writing of the manuscript.
Received 14 August 2000; revised 2 November 2000;
accepted 6 November 2000
in the maternal serum leptin concentration occurs, which is
followed by a sharp decrease immediately after delivery
(Butte et al, 1997; Hardie et al, 1997; Sattar et al, 1998;
Schrubing et al, 1998). Several studies have demonstrated
that, aside from adipose tissue, the human placenta also
synthesizes leptin (Masuzaki et al, 1997; SenÄaris et al,
1997). Hormones like human chorionic gonadotrophin
(hCG), luteinizing hormone (LH), estradiol and insulin
may promote leptin release from maternal adipocytes and
contribute to the hyperleptinemia (Hardie et al, 1997;
Lepercq et al, 1998; Licinio et al, 1998; Sivan et al,
1998). The exact role of this hyperleptinemia during
pregnancy is not understood. It has been proposed that
the pregnancy-associated increase in leptin concentration is
important for modulating maternal and fetal substrate
availability and supply (Chehab, 1997; Mounzih et al,
1998; Schrubing et al, 2000).
Recently, Cha and Jones (1998) reported that the dietary
intake of polyunsaturated fatty acids might increase plasma
leptin levels. They found 60% higher leptin concentrations
Leptin and phospholipid fatty acids during pregnancy and lactation
P Rump et al
in rats fed ®sh oil or saf¯ower oil relative to rats fed beef
tallow. The authors speculated that the consumption of
long-chain polyunsaturated fatty acids (LCPUFAs) of the
n-3 family especially increases leptin synthesis and secretion. On the other hand, lower plasma leptin concentrations
have been found in mice fed diets rich in n-3 LCPUFAs
(Hun et al, 1999). In diabetic women, the combination of
waist:hip ratio and dietary intake of docosahexaenoic acid
(22:6n-3) accounted for 42% of the variance in plasma
leptin concentration (Rojo-MartõÂnez et al, 2000). Moreover,
the expression of the leptin gene in intra-abdominal adipose
tissue of rats seems to be regulated by n-3 fatty acids,
particularly by docosahexaenoic acid (Raclot et al, 1997).
These ®ndings indicate an interaction between n-3
LCPUFA metabolism and plasma leptin concentrations.
During the course of pregnancy, the n-3 fatty acid
composition of maternal plasma phospholipids changes
(Al et al, 1995). Independent of dietary intake, the proportion of docosahexaenoic acid increases during the ®rst 16 ±
22 weeks of pregnancy and subsequently decreases until
delivery (Al et al, 1995; Otto et al, 2000a). During the
postpartum period, the proportion of docosahexaenoic acid
decreases further and this decline is even more pronounced
in lactating women (Otto et al, 2000b). We considered it of
interest to investigate whether these alterations in docosahexaenoic acid concentrations are related to the changes in
plasma leptin levels. For this reason, we conducted this
explorative study and investigated the relation between
leptin concentrations and the docosahexaenoic acid content
of plasma phospholipids in women during pregnancy and
lactation.
Methods
Subjects and design
The study subjects were all participants of two independent
longitudinal observational studies, designed to investigate
the changes in the biochemical essential fatty acid status of
women during early pregnancy or the postpartum period
(Otto et al, 2000a,b). These studies were conducted
between 1996 and 1999. The Medical Ethics Committee
of the University Hospital in Maastricht approved both
study protocols, and an informed consent was obtained
from all participants.
Study 1. To study changes in essential fatty acid status
during early pregnancy, women planning to become pregnant were recruited by means of advertisements in local
newspapers. Only healthy women, not suffering from any
metabolic, cardiovascular, neurological or renal disorder,
were enrolled. From the 67 respondents, six women were
already pregnant, 11 chose not to participate, 20 dropped
out for various reasons (such as lack of motivation or
miscarriage) and six did not conceive within the study
period. A non-fasting blood sample was collected on the
®rst or second day of each menstrual period. When menstruation did not occur at the expected time, a blood sample
was obtained anyway. As a result, blood was collected 4 ± 5
weeks after the ®rst day of the last menstrual period (LMP)
and thus approximately 2 ± 3 weeks after conception, when
pregnancy was con®rmed. Further sampling time points
were 6, 8 and 10 weeks since the beginning of the LMP. Of
the 24 women who completed the study, blood samples
from 21 subjects were available for the present analysis.
245
Study 2. For the second study, healthy pregnant women
were recruited through midwife practices in the surrounding area of Maastricht. Inclusion criteria were: a pregnancy
duration between 36 and 37 weeks since the ®rst day of the
LMP and absence of any metabolic, cardiovascular (including hypertension), neurological or renal disorder. In addition, women who used any medication other than
multivitamin or iron supplements and those who had a
multiple pregnancy were excluded. Of the 68 women
enrolled, six did not deliver at term, two received a blood
transfusion and three stopped their participation during the
postpartum period, leaving data from 57 women for analysis. Of these subjects, 22 choose to bottle-feed their infant
(non-lactating group) and 35 breast-fed their child (lactating group). Non-fasting blood samples collected during
home visits at study entry, 2 days after delivery and
subsequently 1, 2, 4, and 8 weeks after parturition were
used during the present study. Four women stopped breastfeeding their infant within this period (three 2 weeks after
delivery, one 4 weeks after delivery).
Dietary intake of fatty acids
A food frequency questionnaire (FFQ) was used to assess
dietary fatty acid intake as described before (Al et al, 1996;
Otto et al, 2000a). Dietary intake was determined twice
during study 1. The ®rst FFQ was sent before pregnancy
and the second one at the end of the study period. Because
there were no major differences in dietary intake between
these two measurements (Otto et al, 2000a), the average
intake was calculated and used. During study 2, the dietary
intake of fatty acids determined 4 weeks after delivery was
used. Because the FFQ was returned incomplete or not
returned at all, no intake data was available for eight
subjects (one in study 1, seven in study 2).
Blood collection and laboratory analyses
Blood was collected in EDTA-containing tubes at the
reported time points. Plasma was separated from blood
cells by centrifugation and stored under nitrogen at 780 C
until analysis. The fatty acid composition of plasma phospholipids was determined by capillary gas-liquid chromatography as described before (Otto et al, 2000a,b). Fatty
acid concentrations are reported in mg=l plasma or as
percentage of total fatty acids (% wt=wt). Detailed information on the longitudinal changes in the fatty acid pro®le
of plasma phospholipids during both study periods have
been reported before (Otto et al, 2000a,b).
Plasma leptin concentration was measured using a
commercial human leptin radioimmunoassay kit (Linco
Research, St Charles, MO, USA) according to the
European Journal of Clinical Nutrition
Leptin and phospholipid fatty acids during pregnancy and lactation
P Rump et al
246
manufacturer's instructions. To investigate the effect of
storage at 780 C and of multiple freeze ± thaw cycles on
plasma leptin levels, spare blood samples of 10 pregnant
women collected during a previous project were analyzed.
After 8 y of storage, leptin concentrations were within
a physiological range (mean leptin concentration was
18.6 3.3 mg=l at 13 weeks since the LMP) and related to
both body mass and body mass index (r ˆ 0.84, P ˆ 0.003
and r ˆ 0.82, P ˆ 0.007, respectively). Additional cycles of
freezing and thawing of these samples did not in¯uence
leptin concentrations signi®cantly (not shown). These ®ndings indicate that leptin is stable even after a long time of
storage at 780 C under our conditions, and con®rm the
results of Tamura et al, 1998, who analyzed serum stored
for more than nine years.
Statistical methods
Values are reported as mean s.e.m. Within groups, differences between time points were evaluated by paired Student's t-tests. Unpaired Student's t-tests were applied to
study differences between groups. Relations between variables were analyzed with simple, multiple and stepwise
regression models. Changes in plasma fatty acid levels and
leptin concentrations in time were evaluated with repeated
measures ANOVA. Differences between lactating and nonlactating women during the postpartum period were examined by the group time interaction factor in the repeated
measures ANOVA models. Because of a skewed distribution of leptin concentration, natural log-transformed data
were used during the analyses when appropriate. A twotailed P-value < 0.05 was considered statistically signi®cant. All statistical analyses were performed using the
StatView version 4.5 statistical computer program
(Abacus Concepts Inc., Berkeley, CA, USA).
Results
Body weight, body mass index and plasma leptin
concentration
Age, height, pre-pregnancy weight and pre-pregnancy BMI
were similar in both study groups. Body weight and body
mass index (BMI) increased during the ®rst 10 weeks of
pregnancy (P < 0.02). During the postpartum period, body
weight and BMI decreased (P < 0.001). Postpartum body
weight and BMI were slightly higher than the self-reported
pregravid values (P < 0.001), indicating weight retention.
Body weight (not shown) and BMI were positively related
to plasma leptin concentration in pregnant women
(r ˆ 0.70, P < 0.0001) and in non-pregnant women
(r ˆ 0.80, P < 0.0001). Mean plasma leptin concentration
at study entry was 12.1 1.8 mg=l in the non-pregnant
women of study 1 and 19.1 1.5 mg=l in the pregnant
women of study 2. Independent of BMI, plasma leptin
concentrations were higher in pregnant women than in nonpregnant women (P < 0.0001). In non-lactating women, the
amount of weight retained after delivery was positively
related to plasma leptin concentrations measured at study
European Journal of Clinical Nutrition
entry (r ˆ 0.46, P ˆ 0.04). This relation was not statistically
signi®cant in lactating women.
Plasma leptin concentration and the dietary intake of fatty
acids
The dietary intake of n-3 fatty acids, including docosahexaenoic acid, did not signi®cantly differ between the two
study populations (not shown). Plasma leptin concentration
was negatively related to the intake of n-3 fatty acids
(r ˆ 70.38, P ˆ 0.007) in the women of study 2 only.
When studied separately, this negative relation was present
in lactating women (r ˆ 70.37, P ˆ 0.04) but not in nonlactating women (r ˆ 0.008, P ˆ 0.98). No statistically
signi®cant relation was found between plasma leptin
levels and the dietary intake of n-3 fatty acids after
adjustment for pre-pregnancy BMI.
Leptin concentration and the fatty acid composition of
plasma phospholipids
Observations during early pregnancy (study 1). The time
course of leptin concentration during early pregnancy is
shown in Figure 1. A rapid increase was observed. Leptin
concentrations measured 4 weeks after the ®rst day of the
LMP were signi®cantly higher than the pre-pregnant values
(P ˆ 0.02). This observation demonstrates that the increase
in leptin levels had already started within the ®rst 2 ± 3
weeks after conception. A similar and almost parallel rapid
increase was observed for the docosahexaenoic acid concentration in plasma phospholipids (Figure 1). Four weeks
after the LMP, both the proportion (% wt=wt) and the
absolute concentration (mg=l) of docosahexaenoic acid
were signi®cantly higher than before pregnancy (P ˆ 0.02
and P ˆ 0.01, respectively). A much slower increase was
seen for the total amount of phospholipid-associated fatty
acids (Figure 1). This increase was signi®cant 10 weeks
after the LMP only (P ˆ 0.002).
A positive cross-sectional association between leptin
concentration and the absolute concentration (mg=l) of
docosahexaenoic acid in plasma phospholipids was present
6 weeks after the LMP (r ˆ 0.55, P ˆ 0.008) and 8 weeks
after the LMP (r ˆ 0.47, P ˆ 0.03). Associations at other
sampling points were not statistically signi®cant. The
proportion of docosahexaenoic acid (% wt=wt) in plasma
phospholipids did not relate to leptin concentrations at all,
neither before pregnancy nor at any other time point. More
consistent were the relations between leptin concentration
and the total amount of phospholipid-associated fatty acids
in plasma (Table 1). Similar associations were found
between the total amount of phospholipid-associated fatty
acids and pre-pregnancy BMI (Table 1). When a stepwise
regression procedure was performed, the average amount of
total phospholipid-associated fatty acids was predicted by
the average leptin concentration (r2 ˆ 0.36, P ˆ 0.005),
displacing average BMI.
Studying the relation between delta leptin concentration
(difference between the value at week 10 and the prepregnant value) and delta total phospholipid-associated
fatty acids, a weak positive but non-signi®cant association
Leptin and phospholipid fatty acids during pregnancy and lactation
P Rump et al
docosahexaenoic acid in plasma phospholipids (r ˆ 0.11,
P ˆ 0.63).
Figure 1 Leptin concentration, total amount of phospholipid-associated
fatty acids and the phospholipid-esteri®ed docosahexaenoic acid (22:6n-3)
concentration in plasma of women during early pregnancy (study 1,
n ˆ 21). Pregnancy duration is reported in weeks since the ®rst day of
the last menstrual period (LMP). Because of a skewed distribution of leptin
concentrations, natural log transformed data were used. Values are mean
s.e.m. The reported P-values indicate a signi®cant change in time
(repeated measures ANOVA).
was seen (r ˆ 0.38, P ˆ 0.09). Similarly, a positive trend
between delta phospholipid docosahexaenoic acid concentration (mg=l) and delta leptin levels was observed
(r ˆ 0.38, P ˆ 0.09). Delta leptin concentration did not
relate to the change in the proportion (% wt=wt) of
247
Observations during late pregnancy and the postpartum
period (study 2). The time course of leptin concentration
during late pregnancy and the postpartum period is shown
in Figure 2. After parturition, leptin concentration
decreased quickly. The lowest leptin levels were measured
one week after delivery. During the subsequent 3 weeks,
leptin levels increased and reached values close to those
measured before pregnancy in the women of study 1. A
much slower decrease was observed for the total amount of
phospholipid-associated fatty acids and the phospholipidesteri®ed docosahexaenoic acid concentrations (mg=l and
% wt=wt) in plasma of women during the postpartum
period (Figure 2).
Unlike in study 1, no signi®cant cross-sectional associations between plasma leptin levels and the total amount of
phospholipid-associated fatty acids or the phospholipid
docosahexaenoic acid concentrations (mg=l and % wt=wt)
were present. Even when plasma leptin concentrations were
stable, 8 weeks after parturition, no association between
leptin levels and the total amount of phospholipidassociated fatty acids was seen. Furthermore, no relation
was found between the total amount of phospholipidassociated fatty acids and pre-pregnancy BMI either. The
associations between leptin concentrations and pre-pregnancy BMI remained, during pregnancy and during the
postpartum period (not shown).
As indicated by the time group interaction factors of
the ANOVA model, the postpartum changes in leptin
concentration did not signi®cantly differ between lactating
women and non-lactating women. Although leptin concentrations were signi®cantly higher in non-lactating women
when compared to lactating women (P ˆ 0.0009), this
difference was already seen before delivery. Adjustment
for this difference in initial leptin concentration did not
alter the results. There was still no statistically signi®cant
difference in the postpartum change of leptin concentrations between the two groups. Excluding the four women
who stopped breast-feeding their infant within the study
period did not in¯uence the outcomes either.
The decrease in the proportion (% wt=wt) of docosahexaenoic acid was more pronounced in lactating women than
in non-lactating women, whereas the changes in the total
amount of phospholipid-associated fatty acids and phopholipid docosahexaenoic acid concentration (mg=l) did not
differ (reported before in Otto et al, 2000b). Neither the
changes in phospholipid docosahexaenoic acid concentrations (mg=l and % wt=wt) nor the change in the
total amount of phospholipid-associated fatty acids were
signi®cantly related to the change in plasma leptin levels.
Relations between leptin concentration and other
phospholipid-associated fatty acids
In rats (Cha & Jones, 1998) and diabetic patients (RojoMartõÂnez et al, 2000), leptin concentrations have also been
related to other fatty acids than docosahexaenoic acid.
European Journal of Clinical Nutrition
Leptin and phospholipid fatty acids during pregnancy and lactation
P Rump et al
248
Table 1 Results of linear regression analyses between the total amount of phospholipid-associated fatty acids and
leptin concentration and between the total amount of phospholipid-associated fatty acids and body mass index (BMI),
before and during early pregnancy (study 1; n ˆ 21)
BMI (kg=m2)
Leptin (mg=l)
Time point
Before pregnancy
4 weeks since LMP
6 weeks since LMP
8 weeks since LMP
10 weeks since LMP
ba
s.e.
r
P-value
bb
s.e.
r
P-value
9.6
7.4
8.7
11.4
10.5
4.0
4.6
2.3
3.3
3.8
0.48
0.35
0.66
0.62
0.53
0.03
0.12
0.001
0.003
0.01
16.3
16.7
19.6
29.1
20.4
7.4
10.7
6.8
8.4
10.5
0.47
0.35
0.57
0.64
0.43
0.04
0.14
0.009
0.002
0.07
Pregnancy duration is reported in weeks since the ®rst day of the last menstrual period (LMP).
Difference in total phospholipid-associated fatty acids (mg=l) per unit difference in plasma leptin concentration.
b
Difference in total phospholipid-associated fatty acids (mg=l) per unit difference in pre-pregnant BMI (body mass
index).
a
Therefore, we also explored potential associations between
leptin levels and the proportions (% wt=wt) of palmitic acid
(16:0), stearic acid (18:0), oleic acid (18:1n-9), linoleic acid
(18:2n-6), arachidonic acid (20:4n-6) and eicosapentanoic
acid (20:5n-3) in plasma phospholipids. Weak and inconsistent associations were found. In the pregnant women
of study 2, leptin concentrations were positively related
to the proportion of oleic acid (r ˆ 0.31, P ˆ 0.02) and
negatively to the proportion of linoleic acid (r ˆ 70.34,
P ˆ 0.01), at study entry. This negative relation with
linoleic acid concentration was also found two weeks
after delivery (r ˆ 70.33, P ˆ 0.01). At the other time
points of measurement, however, no such relations were
found.
Discussion
As in many other studies (Butte et al, 1997; Lage et al,
1999; Sattar et al, 1998; Schrubing et al, 1998; Tamura
et al, 1998), plasma leptin concentrations were signi®cantly
higher in pregnant women when compared to non-pregnant
women. Our study further indicated that this pregnancyrelated increase in leptin concentration starts within the ®rst
2 ± 3 weeks after conception. It is suggested that the
placenta is a major source of maternal leptin during
pregnancy (Masuzaki et al, 1997; SenÄaris et al, 1997).
Considering the fast increase in leptin concentration during
the ®rst weeks of pregnancy, other sources of leptin might
be involved. According to Sivan and colleagues (Sivan
et al, 1998), hormones like human chorionic gonadotropin
(produced by the conceptus during early pregnancy) may
stimulate the release of leptin from maternal adipocytes and
contribute to the hyperleptinemia.
In the present study, plasma leptin concentration was
negatively related to the intake of n-3 fatty acids, but only
after delivery in lactating women. Although the changes in
the phospholipid-esteri®ed docosahexaenoic acid concentration (mg=l and % wt=wt) almost paralleled those of
leptin concentration, they did not seem to be related.
Positive associations between concentrations of docosahexaenoic acid and leptin levels were found during early
European Journal of Clinical Nutrition
pregnancy, but they were inconsistent and only present
when the docosahexaenoic acid concentration was
expressed in absolute values (mg=l). During early pregnancy, no relation was found between leptin concentration
and the proportion of any other investigated fatty acid
either. Moreover, neither the fatty acid composition of
plasma phospholipids nor the dietary intake of fatty acids
were related to leptin levels before the women were
pregnant. These ®ndings differ from previous observations
in non-pregnant diabetic women (Rojo-MartõÂnez et al,
2000).
Interestingly, more consistent relations were found
between leptin concentration and the total amount of
phospholipid-associated fatty acids during the ®rst 10
weeks of pregnancy. In a stepwise regression analysis,
leptin explained 36% of the variance in the total amount
of phospholipid-associated fatty acids, displacing body
mass index. Except for sphingomyelins, phospholipids
generally contain two fatty acid molecules. Unless major
changes in the composition of plasma phospholipid classes
occur, the total amount of phospholipid-associated fatty
acids mainly re¯ects the plasma phospholipid pool size.
Therefore, our ®ndings suggest that the phospholipid
pool size rather than its composition is either directly or
indirectly related to leptin concentrations.
The maternal liver is regarded as the main source of
plasma phospholipids and associated fatty acids during
pregnancy. Both an increased phospholipid synthesis and
an increased release of very low-density lipoprotein
(VLDL) particles are considered to be involved (Herrera,
2000; Neville, 1999). Placenta-derived hormones such as
estrogens play an important role in this process (Alverez
et al, 1996; Hachey, 1994). Whether leptin (derived from
the placenta or from maternal adipocytes) has any in¯uence
on hepatic phospholipid synthesis or VLDL release is
unknown and remains to be explored.
The most substantial increases in plasma phospholipids
and other lipid fractions occur after the ®rst 10 weeks of
pregnancy (Desoye et al, 1987; Potter & Nestel, 1979).
When we studied the relations between pre-pregnancy
BMI, leptin concentration and the amount of phospholipid-associated fatty acids at 36 weeks of gestation and
Leptin and phospholipid fatty acids during pregnancy and lactation
P Rump et al
Figure 2 Leptin concentration, total amount of phospholipid-associated
fatty acids and the phospholipid-esteri®ed docosahexaenoic acid (22:6n-3)
concentration in plasma of women during the postpartum period (study 2,
n ˆ 57). Mean pregnancy duration was 36.4 0.1 weeks at entry and
40.3 0.2 weeks at delivery (D). Because of a skewed distribution of
leptin concentrations, natural log-transformed data were used. Values are
mean s.e.m. The reported P-values indicate a signi®cant change in time
(repeated measures ANOVA).
during the subsequent postpartum period, the total amount
of fatty acids in plasma phospholipids no longer related to
either BMI or leptin concentration. It seems that the
relation between leptin, BMI and the phospholipid pool
size is `uncoupled' during the course of pregnancy. The
association between BMI and leptin concentrations, however, remained.
An explanation for the lack of an association between
leptin concentration and the total amount of phospholipidassociated fatty acids during late pregnancy could be that
the women became leptin resistant. Many investigators
proposed such a leptin resistant state during pregnancy
(Chehab, 1997; Hardie et al, 1997; Highman et al, 1998;
Mounzih et al, 1998; Sattar et al, 1998; Schrubing et al,
1997). They believe that this putative insensitivity to leptin
could be of physiologic importance. It would support
maternal food intake and the accumulation of fat and
nutrient reserves, which are necessary for optimal fetal
growth during later phases of pregnancy and for lactation.
It is not known whether such a leptin resistant state would
support the development of hyperlipidemia during pregnancy, but it has been suggested that leptin resistance might
lead to obesity syndromes that share the phenotypes of
hypertriglyceridemia, insulin resistance and diabetes
(Unger et al, 1999). The very same phenotypes are
common among pregnant women.
A continuation of leptin insensitivity after delivery
could explain the lack of an association between leptin
levels and the total amount of phospholipid-associated fatty
acids during the postpartum period. As proposed by Stein
et al (1998), such a continuation of leptin resistance could
also explain the observed weight retention. During the
present study, a positive association between leptin concentration at study entry and retained weight after delivery
was found in non-lactating women. However, since no
clinical test is available to determine leptin resistance, the
proposed leptin insensitivity remains speculative.
Leptin is known to circulate in a free as well as a
protein-bound form. The RIA-method used during the
present study measures the total amount of circulating
immunoreactive leptin and does not distinguish between
these two forms, unless combined with gel-exclusion chromatography (Teppa et al, 2000). Recent studies have shown
that the concentrations of both forms of circulating leptin
are elevated during pregnancy (Lewandowski et al, 1999;
Teppa et al, 2000). Free leptin and bound leptin may have
distinct functions (Brabant et al, 2000). Whether free leptin
or bound leptin relates to the plasma phospholipidassociated fatty acids during early pregnancy cannot be
derived from our results and thus needs further elucidation.
Therefore, it seems advisable to measure both forms of
circulating leptin during future studies.
In summary, the total amount of plasma phospholipidassociated fatty acids (rather than the proportion of any
speci®c fatty acid such as docosahexaenoic acid) is related
to both BMI and leptin concentration, before and during
early pregnancy. These associations are no longer present
during late pregnancy and the ®rst two months after
delivery. Although it seems that leptin is not associated
to the pregnancy-related changes in the concentrations of
plasma phospholipid-associated fatty acids directly, the
involvement of a leptin resistant state during pregnancy
cannot be excluded.
249
European Journal of Clinical Nutrition
Leptin and phospholipid fatty acids during pregnancy and lactation
P Rump et al
250
Acknowledgements ÐThe authors thank Hasibe Aydeniz and Joan Senden
for their technical assistance. Most of all, we thank the participating
women for their cooperation.
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