Maternal recreational physical activity is associated with plasma leptin concentrations in early pregnancy

Y. Ning1,2, M.A. Williams1,2,4, C.L. Butler1,2, M. Muy-Rivera1, I.O. Frederick1 and T.K. Sorensen1,3

1 Center for Perinatal Studies, Swedish Medical Center, Seattle, Washington, 2 Department of Epidemiology, University of Washington School of Public Health and Community Medicine, Seattle, Washington and 3 Obstetrix Medical Group, Seattle, Washington, USA

4 To whom correspondence should be addressed at: Center for Perinatal Studies (Suite 4 North), Swedish Medical Center, 747 Broadway, Seattle, WA 98122, USA. Email: mwilliam{at}u.washington.edu


    Abstract
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
BACKGROUND: A limited amount of literature suggests that plasma leptin concentrations are reduced with habitual physical activity in men and non-pregnant women. We investigated the relationship between maternal physical activity and plasma leptin during early pregnancy. METHODS: The study population included 879 normotensive, non-diabetic pregnant women who reported physical activity type, frequency, and duration in early pregnancy. Plasma leptin, measured in blood samples collected <16 weeks gestation, were determined using enzyme immunoassays. Weekly duration (h/week) and energy expended on recreational physical activity [metabolic equivalent score (MET)-h/week] were categorized by tertiles among active women. Physical activity intensity was categorized as none, moderate (<6 MET) and vigorous (≥6 MET). Differences in leptin concentrations across categories were estimated using linear regression procedures. RESULTS: Mean leptin was 5.8 ng/ml lower among active versus inactive women (P=0.001). Mean leptin was lower among women in the highest levels (>12.8 h/week) of time performing physical activity (–8.1 ng/ml, P<0.001) and energy expenditure (>70.4 MET-h/week) (–8.3 ng/ml, P=0.001) compared with inactive women. Leptin was inversely associated with the intensity of physical activity. CONCLUSIONS: Our findings are consistent with other reports suggesting an independent inverse relationship between habitual physical activity and leptin concentrations. Our findings extend the literature to include pregnant women.

Key words: body mass index/leptin/obesity/physical activity/pregnancy


    Introduction
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Leptin, an adipocyte-derived hormone that is also produced by the placenta in humans (Zhang et al., 1994Go; Halaas et al., 1995Go; Masuzaki et al., 1997Go), plays an integral role in endocrine regulation of metabolism. Leptin is now recognized as an integrative hormone that responds to and regulates different endocrine pathways with direct metabolic effects on peripheral tissues (Sandoval and Davis, 2003Go). Leptin released into peripheral circulation is thought to regulate fat mass and to reduce food intake and stimulate thermogenesis (Halaas et al., 1995Go). Activation of the sympathetic nervous system by leptin is considered the primary mechanism mediating an increase in energy expenditure. Obesity is positively associated with plasma leptin concentrations, with secretion being in proportion to adipocyte size and number. Weight loss, fasting and starvation are known to induce reductions in leptin concentrations. Conversely, leptin concentrations are increased with weight gain and systemic inflammation (Grunfeld et al., 1996Go; Havel et al., 1996Go; Jequier, 2002Go). Changes in circulating leptin concentrations in pregnant women coincide with changes in maternal fat stores and energy metabolism. Maternal leptin concentrations increase 2–3-fold above non-pregnant concentrations, with the peak occurring in the late mid-trimester (Schubring et al., 1998Go). For instance, investigators have reported that serum total leptin concentrations were statistically significantly higher in pregnant women (33.8±4.1 ng/ml) as compared with non-pregnant women (15.2.8±1.8 ng/ml, P=0.002) (Teppa et al., 2000Go). Results from clinical studies indicate that pregnancy-associated increases in maternal plasma leptin are, in part, attributable to an up-regulation of adipocyte synthesis and release of leptin in the presence of insulin resistance and hyperinsulinaemia (Laivuori et al., 2000Go). Additionally, investigators have shown that placental leptin synthesis is increased in the presence of hypoxaemia (Mise et al., 1998Go). Adipose tissue mass, weight change, inflammation and pregnancy only partially explain the large intra-individual variation in plasma leptin concentrations. Consequently, considerable effort has been dedicated to identifying genetic and other factors that influence leptin synthesis and release into the peripheral circulation (Havel et al., 1996Go; De Silva et al., 1998Go; Reseland et al., 2001Go; Jequier, 2002Go; Lakka et al., 2004Go); an emerging literature suggests that elevated leptin concentrations in early pregnancy are predictive of pre-eclampsia (Williams et al., 1999Go; Poston, 2002Go; Ning et al., 2004Go) and gestational diabetes mellitus (Qiu et al., 2004Go).

Two independent groups of investigators have reported that recreational physical activity during pregnancy is associated with a reduced risk of pre-eclampsia (Marcoux et al., 1989Go; Sorensen et al., 2003Go). Recently, investigators reported that physically active women who continued to exercise during pregnancy experienced a 40–70% reduced risk of gestational diabetes mellitus as compared with sedentary women (Dempsey et al., 2004Go). Physical activity, because of its role in long-term regulation of body weight, fat mass, and capacity to increase resting metabolic rate (Maehlum et al., 1986Go; Bahr, 1992), was postulated to be a determinant of leptin concentrations (Considine, 1997Go). This thesis is supported by results from animal studies (Zheng et al., 1996Go; Bramlett et al., 1999Go) and short-term exercise training studies in humans (Racette et al., 1997Go; Dirlewanger et al., 1999Go; Dulcos et al., 1999Go; Reseland et al., 2001Go; Koutsari et al., 2003Go). To date, only a few investigators have studied the effects of habitual physical activity on leptin concentrations, and results have been inconsistent (De Silva et al., 1998Go; Donahue et al., 1999Go; Ruige et al., 1999Go; Franks et al., 2003Go). We are unaware of published studies that have assessed the influence of habitual physical activity on plasma leptin concentrations in pregnant women.

In light of this gap in knowledge, and given the fact that leptin concentrations are profoundly altered in pregnant women, particularly women with gestational diabetes and pre-eclampsia (disorders that have been shown to be reduced in physically active inactive women), we conducted the present study. We sought to assess the extent to which, if at all, maternal plasma leptin concentrations in early pregnancy are reduced in women who regularly engage in recreational physical activity as compared to their less active counterparts. Detailed assessments of maternal physical activity during early pregnancy allowed us to determine whether the amount and intensity of recreational physical activity are independent determinants of plasma leptin concentrations in early pregnancy.

Given that habitual exercise during pregnancy is associated with improved insulin sensitivity, reduced blood pressure, and improved plasma lipid and lipoprotein concentrations (Clapp and Capeless, 1991Go; Yeo et al., 2000Go; Butler et al., 2004Go), we hypothesized that similar benefits would be found when leptin was assessed.


    Materials and methods
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The Omega study: overview and analytical population
The population for the present analysis was drawn from participants of the ongoing Omega study, which is designed to examine maternal dietary and lifestyle risk factors of pre-eclampsia and gestational diabetes mellitus. The study population is comprised of women attending prenatal care clinics affiliated with Swedish Medical Center and Tacoma General Hospital in Seattle and Tacoma, Washington, respectively. Women who initiated prenatal care prior to 16 weeks gestation were eligible for the study. Women were ineligible if they were aged <18 years, did not speak and read English, did not plan to carry the pregnancy to term, did not plan to deliver at either of the two research hospitals, and/or were past 16 weeks gestation. Participants were invited to provide blood samples and to participate in an in-person interview. Maternal and infant records were reviewed and data were abstracted. The procedures used in this study were in agreement with the protocols approved by the Institutional Review Boards of Swedish Medical Center and Tacoma General Hospital respectively. All participants provided written informed consent.

The analytical study population for this report is derived from participants who were enrolled in the Omega study between 1996 and 2000. During this period, 1219 eligible women were approached and 1000 (~82%) agreed to participate. During this enrolment period, we primarily approached and enrolled nulliparous women. Multiparous women were approached and enrolled on a personnel available basis. Women found to have chronic hypertension (n=46), pre-gestational diabetes mellitus (n=5), and both conditions (n=1) were excluded. Also excluded were those women with missing information on recreational physical activity (n=17) and with insufficient plasma required for determining plasma leptin concentrations (n=52). A sample of 879 women remained for analysis.

Data collection and physical activity assessment
At the time of enrolment in the Omega study (12.7 weeks gestation, on average), a 45–60 min structured questionnaire was administered by a trained interviewer. Information on sociodemographic characteristics, medical and reproductive histories, and lifestyle characteristics was collected. Women were also asked to list the recreational activities in which they had participated during the previous 7 days, which comprised the physical activity assessment period. For each activity, women were asked the number of hours spent performing the activity, on weekdays and weekend days, separately. Similar questions were asked to collect information on physical activity during the year before pregnancy. Questions were derived from the Stanford Seven-Day Physical Activity Recall and the Minnesota Leisure-Time Physical Activity Questionnaire, which have been validated in men and non-pregnant women (Jacobs et al., 1993Go; Richardson et al., 1994Go).

Blood collection and plasma leptin measurements
At or near the time of interview (13.2 weeks gestation, on average), a non-fasting blood sample was collected. Blood was drawn into lavender-top vacutainer tubes containing K3-EDTA (1 mg/ml). The tube was centrifuged at 850 g for 20 min at 4°C to separate red cells, white cells, and plasma. Fractions were aliquoted and stored at –80°C until analysis. Plasma leptin concentrations were measured using an enzyme immunoassay (Diagnostic Systems Laboratory, Inc., USA) with the intra- and inter-assay coefficients of variation both <8%. Leptin concentrations in non-pregnant women have been reported to range from 3.9 to 77.3 ng/ml, with a mean concentration of 20.7 ng/ml in a non-selected laboratory population (Diagnostic Systems Laboratory). All assays were completed without knowledge of maternal physical activity and other characteristics.

Specifications of physical activity variables
We assessed the relationship between plasma leptin concentrations and participation in recreational physical activity during a week in early pregnancy. Women were categorized into two groups: those who had performed any recreational activity during the assessment period (active), and those who had performed none (inactive). We also examined the relationship between plasma leptin concentrations and the following measures of recreational activity: (i) time engaged in physical activity in early pregnancy; (ii) maximum intensity of physical activity in early pregnancy; (iii) energy expended during these activities; (iv) the combined participation in physical activity before and during pregnancy.

To measure the time engaged in physical activity in early pregnancy, the total number of hours spent performing each activity during the assessment period was summed and expressed in hours/week. Inactive women were designated as the referent group. The remaining active women were divided into approximate tertiles according to hours engaged in recreational physical activity. This resulted in four categories of time engaged in physical activity: none, <4.9, 4.9–12.7 and >12.7 h/week.

Physical activity during the previous week was classified by intensity, and the score of the most intense exercise was used to measure maximum intensity. Intensity of physical activity was quantified using a standardized classification procedure that determines the energy costs of specific physical activities (Ainsworth et al., 2000Go). Energy costs for each activity, expressed as metabolic-equivalent (MET) scores, estimate energy expended on each activity. One MET is the ratio of work metabolic rate to a standard resting metabolic rate of 4.18 kJ/kg/h (Ainsworth et al., 2000Go). As the intensity of physical activity increases above that of the resting state, the energy expended in performing an activity (MET) increases. We defined light-intensity activities as those with MET scores of <3. Examples of light activities include croquet and horseback riding. Moderate-intensity activities (3 to <6 MET) include casual swimming and cycling. Vigorous recreational activities (≥6 MET) include jogging, running, lap swimming, and aerobic exercise. Using the MET scores, we classified physically active subjects according to the intensity of their most vigorous activity during the assessment period. We initially constructed four categories of maximum intensity: no activity, and light, moderate and vigorous intensity. However, because only two women reported light intensity (<3 MET), we included them in the group reporting moderate maximum intensity activities.

The total amount of energy expended during recreational activity during the assessment period was measured. Energy expenditure integrates the intensity with the amount of time spent performing each activity. Energy costs for each activity were calculated as described by Ainsworth et al. (2000)Go and expressed in MET. Energy expenditure, expressed as MET-h/week, was calculated by summing the total number of hours spent on each activity in the assessment period, multiplying the result by the activity intensity score, and summing over all reported activities. Inactive women were designated as the referent group. The remaining active women were categorized into approximate tertiles of weekly energy expenditure. The four categories of weekly energy expenditure were as follows: not active, <21.0 MET-h/week, 21.0–70.4 MET-h/week, and >70.4 MET-h/week.

The joint effect of exercise before and during pregnancy was also assessed. We categorized women into four groups based upon their reported activity during a week in early pregnancy and the year before pregnancy. Categories of combined physical activity before and during pregnancy were as follows: inactive during both periods, active before pregnancy only, active during pregnancy only, and active during both periods.

Statistical analysis
We examined frequency distributions of maternal sociodemographic, reproductive, and medical characteristics. We then examined the distribution of plasma leptin and found it approximately normal. We therefore compared differences in mean leptin concentrations across categorical levels of maternal characteristics using independent-sample t-tests, assuming unequal variances. Differences in mean leptin concentrations across measures of physical activity (i.e. any activity, time, maximum intensity, energy expenditure, and activity during and before pregnancy) were also examined.

Multivariable linear regression analyses with robust variances (White, 1980Go) were performed to evaluate the association between various physical activity measures and plasma leptin concentrations. To assess confounding, we entered covariates into a linear regression model sequentially, and then compared the unadjusted and adjusted regression coefficients for physical activity (Rothman and Greenland, 1998Go). Final models included covariates that altered unadjusted coefficients for physical activity by ≥10%, as well as covariates of a priori interest (i.e. maternal age and parity). The following covariates were considered as possible confounders: maternal age (<20, 20–34, 35–39, ≥40 years), race/ethnicity (White, African, Asian and other), marital status (married versus other), educational attainment (≤12 versus >12 years), parity (nulliparous versus parous), smoking during pregnancy (yes versus no), gestational age (weeks) at blood collection (continuous), pre-pregnancy body mass index (BMI) and BMI at the time of blood collection (each BMI variable specified as follows: <20, 20 to <25, 25 to <30, ≥30 kg/m2). Hereinafter, we refer to the latter BMI as ‘early pregnancy BMI’. To assess the potential modifying effects of BMI on the relationships between physical activity and leptin concentrations, we fit linear regression models with interaction terms between each exercise variable and maternal early pregnancy BMI. Adjusted R2 values were calculated to measure the explanatory power of each model, adjusted for degrees of freedom. All analyses were performed using Stata 7.0 statistical software (Stata, College Station, Texas, USA). All continuous variables are presented as mean±SE. All reported P-values are two-tailed.


    Results
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
Table I shows demographic, reproductive and medical characteristics of the 879 women in the study sample. Women were generally White (86.8%), married (88.5%), educated (95.3%, high school or more), and nulliparous (85.2%). Forty-eight per cent reported having a positive first-degree family history of essential hypertension. Approximately 15% of women reported having a positive first-degree family history of diabetes. Ninety per cent of women reported that they engaged in some form of recreational physical activity in the year before pregnancy, and 83.4% reported that they engaged in recreational physical activity during the study pregnancy.


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Table I. Sociodemographic, reproductive and medical characteristics of study participants: The Omega Study, Seattle and Tacoma, Washington, 1996–2000 (n=879)

 
Several maternal characteristics were statistically significantly related to plasma leptin concentrations (Table II). Leptin concentration was higher among women who were African American, multiparous, and among women who had a first-degree family history of diabetes or hypertension. As expected, leptin concentrations increased across increasing categories of maternal early pregnancy BMI. Mean leptin concentrations among women with a BMI ≥30 kg/m2 were higher than the mean concentrations observed in lean (BMI <20 kg/m2) women (55.0±2.1 versus 9.2±0.8 ng/ml, P<0.001).


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Table II. Distributions of plasma leptin concentrations (ng/ml) according to selected covariates: The Omega Study, Seattle and Tacoma, Washington, 1996–2000 (n=879)

 
As shown in Table III, mean leptin concentrations decreased across levels of physical activity during pregnancy. Mean leptin was 25.6±0.7 ng/ml among women who reported participating in any recreational physical activity, compared to 34.1±1.8 ng/ml among inactive women (P<0.001). Among active women, mean leptin concentrations decreased across categories of increasing hours/week engaged in physical activity. For women who exercised ≤4.8, 4.9–12.8, and >12.9 h per week, mean leptin concentrations were 27.6±1.2, 25.4±1.2 and 23.7±1.3 ng/ml respectively. Similar patterns were observed across categories of maximum intensity and energy expended performing physical activity.


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Table III. Distributions of plasma leptin concentrations (ng/ml) according to recreational physical activity in a week during pregnancy and the year before pregnancy: The Omega Study, Seattle and Tacoma, Washington, 1996–2000 (n=879)

 
We also evaluated leptin concentration in women according to whether they were active during one or both periods of observations. When women were classified according to physical activity status during the periods of before and during pregnancy, those reporting activity during both periods had the lowest mean leptin concentrations compared with inactive women (25.2±0.7 versus 29.9±4.0 ng/ml) (Table III). Mean leptin concentrations were higher among those performing physical activity only in the year before pregnancy (35.1±2.0 ng/ml) and among those performing physical activity only during the study pregnancy (30.9±3.3 ng/ml). These differences, however, did not reach statistical significance. A larger, more powerful study is needed to evaluate maternal leptin concentrations in relation to her activity level over the two time periods.

As shown in Table IV, associations between leptin concentration and measures of physical activity remained after adjustment for potential confounding by maternal age, race/ethnicity, parity and smoking status (Model 2). Notably, the associations remained statistically significant, though somewhat attenuated, after maternal early pregnancy BMI was included in the multivariable model (Model 3). After controlling for confounders, any physical activity during pregnancy was associated with lower plasma concentrations on average (6.0±1.6 ng/ml, P=0.001). The model explained 42% of the variance in leptin concentration (adjusted R2=0.42). Active women reporting the lowest level of energy expended on recreational physical activity (<20.9 MET-h/week) had leptin concentrations that were 3.5±1.7 ng/ml lower, on average, compared with concentrations observed among inactive women (P=0.040). Mean leptin concentrations were 6.1±1.7 ng/ml lower among women in the middle level (21.0–70.4 MET-h/week) (P<0.001), and 8.5±1.8 ng/ml lower among women in the highest level of expended energy category (P<0.001). Similar relationships were observed between plasma leptin concentrations and both the amount of time spent performing physical activity and maximum intensity after adjustment for confounders.


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Table IV. Relationships between measures of physical activity in early pregnancy and plasma leptin concentrations (ng/ml): estimated linear regression coefficients for the participants of the Omega Study, Seattle and Tacoma, Washington, 1996–2000 (n=879)

 
We next evaluated the association between leptin concentration and physical activity according to maternal early pregnancy BMI. We fitted linear models with interaction terms between physical activity energy expenditure and BMI categories. Figure 1 shows maternal mean leptin concentrations across levels of energy expenditure, within groups defined by early pregnancy BMI. Values are representative of nulliparous, white, non-smokers aged <35 years. Leptin concentrations tended to be inversely associated with physical activity energy expenditure in lean, normal weight, overweight and obese women, alike.



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Figure 1. Mean adjusted leptin concentrations reported according to maternal recreational physical activity energy expenditure (MET-h/week) and early pregnancy body mass index (BMI, kg/m2). Values are representative of nulliparous, white, non-smoking women who are <35 years of age.

 

    Discussion
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
In this cross-sectional study of recreational physical activity and leptin, we observed statistically significant inverse associations between multiple measures of maternal physical activity during pregnancy (e.g. duration, intensity and energy expenditure on recreational physical activity) and plasma leptin concentrations. The associations were independent of maternal early pregnancy BMI and other potential confounders. In this population, physically active lean women had the lowest plasma leptin concentrations in early pregnancy.

To our knowledge there have been no published studies that have assessed the extent to which maternal plasma leptin concentrations in pregnancy are associated with habitual physical activity performed before and/or during pregnancy. Our results, however, are consistent with most, though not all, previously published observational studies that have evaluated the impact of habitual physical activity on leptin concentrations in men and non-pregnant women (De Silva et al., 1998Go; Donahue et al., 1999Go; Ruige et al., 1999Go; Franks et al., 2003Go). Recently, Franks et al. (2003)Go, in their population-based cohort study of 758 Caucasian men and women in Ely, Cambridgeshire, UK, reported that plasma leptin concentrations were statistically significantly associated with physical activity energy expenditure ({beta}=–0.26, P<0.001) after adjustment for BMI. These results were largely similar to those reported by Ruige et al. (1999)Go and Donahue et al. (1999)Go, who reported that plasma leptin concentrations were independently inversely associated with self-reported habitual physical activity. Our results and those of others (Donahue et al., 1999Go; Ruige et al., 1999Go; Franks et al., 2003Go) are inconsistent with the report by De Silva et al. (1998)Go who observed no independent association between leptin concentrations and physical activity in their population-based study of 359 Austrian women.

Several limitations merit discussion and consideration. First, the cross-sectional design of our study and the fact that we did not directly measure maternal adipose tissue mass during pregnancy limited our ability to infer the temporal relationship between physical activity, adipose tissue mass and plasma leptin concentrations according to maternal adiposity in early pregnancy. Prospective studies of pregnant women that include objective measures of maternal adipose tissue mass are needed to demonstrate more conclusively these potential causal relationships. Second, a single measurement of plasma leptin may be susceptible to short-term variations, and thus is not likely to provide a time-integrated measure of maternal leptin status during early pregnancy. Consequently, results from our study, with only one measurement of plasma leptin, may have been biased; and this bias is likely to have resulted in an under-estimation of the true relationship between physical activity and plasma leptin concentrations. We are also not able to report on the relationship between maternal physical activity and leptin concentrations later in gestation. Longitudinal studies with serial measurement of maternal plasma leptin concentrations are needed to expand upon our current findings. Third, measurement error from the use of self-reported physical activity is likely to have occurred. However, this error is unlikely to have systematically biased our findings, because the reporting error is not associated with the laboratory determination of maternal plasma leptin concentrations. Misclassification of maternal physical activity status (unrelated to our laboratory measures of maternal plasma leptin concentrations) would have served to underestimate the true association between the two covariates. Fourth, diurnal variation in leptin concentration may have influenced our results. Because subjects were recruited and enrolled while they attended obstetric clinics to receive standard prenatal care, and because prolonged fasting is contraindicated during pregnancy, we were restricted to measuring leptin in non-fasting blood samples. Lastly, our study population was uncommonly active and so inferences from our cohort may not be generalizable to other populations. Only 17% of women reported no recreational physical activity during pregnancy and 10% reported none during the year before pregnancy. In contrast, in a 1998 national survey, 59% of American women aged 18–44 years reported never engaging in physical activity lasting ≥10 min per week (Pleis and Coles, 2002Go).

There are several postulated biological mechanisms for the observed inverse association between physical activity and plasma leptin concentrations (Bornstein, 1997Go; Considine, 1997Go). Some investigators (Kosaki et al., 1996Go; Trayhurn et al., 1998Go; Scriba et al., 2000Go) have noted that exercise-induced modifications of the sympathetic nervous system results in increased concentrations of catecholamines which may attenuate leptin synthesis and release. This thesis is supported by reports from Couillard et al. (2002)Go, which indicate that plasma leptin is reduced after an epinephrine infusion in lean and obese women. Alternatively, physical activity may influence plasma leptin concentrations directly through its impact on leptin synthesis. Results from animal and human studies (Friedman et al., 1997Go; Racette et al., 1997Go) support this thesis. Friedman et al. (1997)Go reported that leptin mRNA expression was reduced in genetically obese rats after exercise training. Moreover, Racette et al. (1997)Go noted that moderate-intensity physical activity resulted in a reduction in abdominal fat leptin synthesis in humans. Lastly, some investigators postulate that improved insulin sensitivity, secondary to physical activity, may influence leptin synthesis and concentrations in circulation, independent of adipose tissue mass (Considine, 1997Go). Whatever the mechanism, results from animal and human studies using diverse methodologies suggest that physical activity is an independent determinant of leptin concentrations in peripheral circulation.

Our results are largely consistent with findings emerging from exercise intervention trials (Racette et al., 1997Go; Reseland et al., 2001Go; Koutsari et al., 2003Go), and the few observational epidemiological studies (Ruige et al., 1999Go; Franks et al., 2003Go) that suggest that physical activity may influence leptin concentrations in peripheral circulation in men and non-pregnant women. Our results extend this growing literature to include pregnant women. Given the central role leptin plays in regulating energy homeostasis through central and peripheral mechanisms, and that pregnancy represents a period of profound alterations in glucose homeostasis and lipid metabolism, it stands to reason that factors that influence leptin synthesis and release in the non-pregnant state may also play a role during pregnancy. Our findings suggest that alterations in maternal leptin concentrations may be achieved with habitual physical activity during pregnancy.

Hyperleptinaemia has emerged as a promising clinical risk factor for pre-eclampsia (Williams et al., 1999Go; Poston, 2002Go; Ning et al., 2004Go) and gestational diabetes mellitus (Qiu et al., 2004Go). Both disorders are inversely associated with maternal physical activity before and/or during pregnancy (Marcoux et al., 1989Go; Sorensen et al., 2003Go; Dempsey et al., 2004Go). At present, little is known about modifiable factors that influence leptin concentrations in maternal circulation during pregnancy and pre-eclampsia risk. Our findings suggest that physical activity, a modifiable factor, influences leptin synthesis and release in pregnancy. If confirmed, physical activity during pregnancy may well be one important component in lifestyle programmes and strategies aimed towards disease prevention and health promotion in all populations, including pregnant women.


    Acknowledgements
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
The authors are indebted to the participants of the Omega Study for their cooperation. They are also grateful for the technical expertise contributed by the staff of the Center for Perinatal Studies, Swedish Medical Center. This research was supported by awards from the National Institutes of Health (HD/HL 32562 and HD/HL 34888).


    References
 Top
 Abstract
 Introduction
 Materials and methods
 Results
 Discussion
 Acknowledgements
 References
 
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Submitted on January 31, 2004; resubmitted on September 24, 2004; accepted on October 21, 2004.





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