Maternal Plasma Leptin Levels Research Articles

Maternal Protein Restriction in Rats Alters Postnatal Growth and Brain Lipid Sensing in Female Offspring.

Perinatal nutrition is a key player in the susceptibility to developing metabolic diseases in adulthood, leading to the concept of "metabolic programming". The aim of this study was to assess the impact of maternal protein restriction during gestation and lactation on glucose homeostasis and eating behaviour in female offspring. Pregnant rats were fed a normal or protein-restricted (PR) diet and followed throughout gestation and lactation. Body weight, glucose homeostasis, and eating behaviour were evaluated in offspring, especially in females. Body weight gain was lower in PR dams during lactation only, despite different food and water intakes throughout gestation and lactation. Plasma concentration of leptin, adiponectin and triglycerides increased drastically before delivery in PR dams in relation to fat deposits. Although all pups had identical birth body weight, PR offspring body weight differed from control offspring around postnatal day 10 and remained lower until adulthood. Offspring glucose homeostasis was mildly impacted by maternal PR, although insulin secretion was reduced for PR rats at adulthood. Food intake, satiety response, and cerebral activation were examined after a lipid preload and demonstrated some differences between the two groups of rats. Maternal PR during gestation and lactation does induce extrauterine growth restriction, accompanied by alterations in maternal plasma leptin and adiponectin levels, which may be involved in programming the alterations in eating behaviour observed in females at adulthood.

Association between plasma leptin and cesarean section after induction of labor: a case control study

BackgroundObesity in pregnancy is common, with more than 50% of pregnant women being overweight or obese. Obesity has been identified as an independent predictor of dysfunctional labor and is associated with increased risk of failed induction of labor resulting in cesarean section. Leptin, an adipokine, is secreted from adipose tissue under the control of the obesity gene. Concentrations of leptin increase with increasing percent body fat due to elevated leptin production from the adipose tissue of obese individuals. Interestingly, the placenta is also a major source of leptin production during pregnancy. Leptin has regulatory effects on neuronal tissue, vascular smooth muscle, and nonvascular smooth muscle systems. It has also been demonstrated that leptin has an inhibitory effect on myometrial contractility with both intensity and frequency of contractions decreased. These findings suggest that leptin may play an important role in dysfunctional labor and be associated with the outcome of induction of labor at term. Our aim is to determine whether maternal plasma leptin concentration is indicative of the outcome of induction of labor at term. We hypothesize that elevated maternal plasma leptin levels are associated with a failed term induction of labor resulting in a cesarean delivery.MethodsIn this case-control study, leptin was measured in 3rd trimester plasma samples. To analyze labor outcomes, 174 women were selected based on having undergone an induction of labor (IOL), (115 women with successful IOL and 59 women with a failed IOL). Plasma samples and clinical information were obtained from the UI Maternal Fetal Tissue Bank (IRB# 200910784). Maternal plasma leptin and total protein concentrations were measured using commercially available assays. Bivariate analyses and logistic regression models were constructed using regression identified clinically significant confounding variables. All variables were tested at significance level of 0.05.ResultsWomen with failed IOL had higher maternal plasma leptin values (0.5 vs 0.3 pg, P = 0.01). These women were more likely to have obesity (mean BMI 32 vs 27 kg/m2, P = 0.0002) as well as require multiple induction methods (93% vs 73%, p = 0.008). Logistic regression showed Bishop score (OR 1.5, p < 0.001), BMI (OR 0.92, P < 0.001), preeclampsia (OR 0.12, P = 0.010), use of multiple methods of induction (OR 0.22, P = 0.008) and leptin (OR 0.42, P = 0.017) were significantly associated with IOL outcome. Specifically, after controlling for BMI, Bishop Score, and preeclampsia, leptin was still predictive of a failed IOL with an odds ratio of 0.47 (P = 0.046). Finally, using leptin as a predictor for fetal outcomes, leptin was also associated with of fetal intolerance of labor, with an odds ratio of 2.3 (P = 0.027). This association remained but failed to meet statistical significance when controlling for successful (IOL) (OR 1.5, P = 0.50).ConclusionsMaternal plasma leptin may be a useful tool for determining which women are likely to have a failed induction of labor and for counseling women about undertaking an induction of labor versus proceeding with cesarean delivery.

Maternal plasma leptin levels in relation to the duration of the active phase of labor.

Obese women have increased leptin levels and longer duration of labor compared with normal-weight women. Leptin has an inhibitory effect on myometrial contractility in vitro. Our purpose was to examine whether maternal leptin levels in active labor were associated with the duration of the active phase of labor. This prospective cohort study included 914 women. Maternal blood samples were collected in active labor. The plasma-leptin concentration was obtained using a direct sandwich-based ELISA. Bivariate and multiple linear regression analyses were used to study the association between leptin levels and the duration of labor. A 1ng/mL increase in maternal plasma leptin was associated with a 0.015hour increase in duration of labor (P<.007). This association was not statistically significant in the adjusted analyses nor when analyzing nulliparous and multiparous women separately. In women with spontaneous labor (n=766) leptin levels were not associated with an increase in duration of labor in the adjusted analyses. There was no significant association between leptin levels and duration of the active phase of labor. Leptin in vivo might display a similar dose-response effect on myometrial contractility as demonstrated in in vitro studies. Future studies need to explore the association between leptin levels and time in labor in obese women with high leptin levels to evaluate a possible dose-response effect.

Abstract P321: Differential Leptin Levels are Associated with Hypertensive Disorders of Pregnancy and Adverse Pregnancy Outcomes

During pregnancy, there are normal changes in maternal body weight and blood pressure that occur. Leptin is found in higher levels in obese individuals and has been demonstrated to have an inhibitory effect on myometrial contractility and to regulate blood pressure. Obesity in pregnancy is common and is associated with many complications, including hypertension in pregnancy, failed induction of labor (IOL), and intrauterine growth restriction. Our goal was to determine whether maternal leptin in a pregnant population is indicative of hypertensive disorders in pregnancy, dysfunctional labor, and whether there is a correlation between cord blood leptin and birthweight. We utilized a case control study with samples from the UI Maternal Fetal Tissue Bank (IRB#200910784). In order to analyze labor outcomes, 168 women were selected based on having undergone an IOL, including 54 failed IOL. Maternal/neonatal characteristics were collected from the medical record. Maternal and cord blood plasma leptin and total protein levels were measured using commercially available ELISAs. Bivariate analyses and logistic regression models were constructed using regression identified clinically-significant confounding variables. All variables were tested at significance level of 0.05. Women with hypertensive disorders in pregnancy, including pregnancy-induced hypertension and preeclampsia, had higher maternal leptin levels (14783 vs. 21440 pg/mL, p=0.049). Women with failed IOL also had higher maternal plasma leptin values (0.5 vs 0.3 leptin/protein [pg/ug], P = 0.01). Birthweight was also correlated with cord blood leptin (correlation coefficient 0.494 P &lt; 0.001). These data suggest that maternal and fetal leptin levels are associated with the central mechanisms responsible for poor pregnancy outcomes.

Maternal obesity (Class I-III), gestational weight gain and maternal leptin levels during and after pregnancy: a prospective cohort study.

BackgroundMaternal obesity is accompanied by maternal and fetal complications during and after pregnancy. The risks seem to increase with degree of obesity. Leptin has been suggested to play a role in the development of obesity related complications. Whether maternal leptin levels differ between obese and morbidly obese women, during and after pregnancy, have to our knowledge not been previously described. Neither has the association between maternal leptin levels and gestational weight gain in obese women. The aim was to evaluate if maternal plasma leptin levels were associated with different degrees of maternal obesity and gestational weight gain.MethodsProspective cohort study including women categorized as obesity class I-III (n = 343) and divided into three gestational weight gain groups (n = 304). Maternal plasma leptin was measured at gestational week 15, 29 and 10 weeks postpartum. Maternal Body Mass Index (BMI) was calculated from early pregnancy weight. Gestational weight gain was calculated using maternal weight in delivery week minus early pregnancy weight. The mean value and confidence interval of plasma-leptin were analysed with a two-way ANOVA model. Interaction effect between BMI and gestational weight gain group was tested with a two-way ANOVA model.ResultsThe mean maternal leptin concentrations were significantly higher in women with obesity class III compared to women in obesity class I, at all times when plasma leptin were measured. The mean leptin concentrations were also significantly higher in women with obesity class II compared to women in obesity class I, except in gestational week 29. There was no difference in mean levels of plasma leptin between the gestational weight gain groups. No significant interaction between BMI and gestational weight gain group was found.ConclusionsPlasma leptin levels during and after pregnancy were associated with obesity class but not with degree of gestational weight gain. These results are in concordance with epidemiological findings where the risk of obstetric complications increases with increased maternal obesity class. The effect on obstetric outcome by degree of gestational weight gain is less pronounced than the adverse effects associated with maternal obesity.

Does leptin predict successful induction of labor?

Obesity in pregnancy is becoming increasingly common and is associated with many pregnancy-related complications such as failed induction of labor (IOL). Leptin, an adipocytokine important in energy homeostasis, is found in higher levels in obese individuals. Leptin has also been demonstrated to have an inhibitory effect on myometrial contractility in vitro. We hypothesize that leptin may play a part in the mechanism of dysfunctional labor. Thus, we sought to compare the maternal plasma leptin levels in women that had a successful vaginal delivery post-IOL vs. those who had a C-section post-IOL.

A maternal high-fat diet in rat pregnancy reduces growth of the fetus and the placental junctional zone, but not placental labyrinth zone growth

Maternal obesity during pregnancy is often characterized by fetal macrosomia but it can also result in fetal growth restriction in a subset of pregnancies. We hypothesized that mechanisms of this growth restriction may include adverse effects of maternal high fat (HF) intake on placental growth and function. Female rats (100 days old) were time-mated and randomly assigned to either a control (Con) or HF diet ad libitum throughout gestation. At E21, dams were killed; litter size and fetal and placental weights were recorded and maternal and fetal samples collected for further analyses. The HF diet resulted in a 54% increase in maternal body weight gain during gestation. In contrast, male and female fetal weights were reduced in HF pregnancies (P &lt; 0.05), as were the weights of the junctional zone of the placenta (P = 0.013), whereas labyrinth zone weights were unaffected. The HF diet increased maternal and fetal plasma leptin levels (P &lt; 0.05), but maternal and fetal insulin and fetal glucose levels were unaffected. Labyrinthine expression of PPARγ and total VEGFa mRNA, both markers of placental vascular development, were unaffected by consumption of the HF diet in placentas of male and female fetuses. Furthermore, maternal HF nutrition did not alter phosphorylated protein levels of either mammalian target of rapamycin or its downstream signaling factor eIF4E binding protein 1 (4E-BP1). These data show that in the rat, maternal HF nutrition results in fetal and placental junctional zone growth restriction, maternal and fetal hyperleptinemia but did not alter gene expression of markers of placental vascular development.

Correlation between maternal first trimester plasma leptin levels and birth weight among normotensive and preeclamptic women

Objective. To determine the connection between maternal first trimester serum leptin levels and newborn weight.Methods. The study included 37 preeclamptic women and 53 normotensive women who considered the control group. Maternal blood samples were withdrawn at 13 weeks of gestation for the measurement of leptin concentrations. Birth weights were transformed to z-scores according to maternal and obstetrical features, based on customised centiles. Non-parametric tests, student's t-test, Pearson's correlation, Spearman's correlation and linear regression analysis were performed in our analysis.Results. Pre-pregnancy body mass index and first trimester maternal plasma leptin levels were significantly higher among women with preeclampsia (p = 0.015 and p < 0.001, respectively). Birth weight z-score was negatively correlated with leptin levels (r = −0.570, p < 0.001), in preeclamptic group and in control group (r = −0.477, p < 0.001). The regression modelling demonstrated a significant negative association between birth weight z-scores and leptin for both groups.Conclusion. Maternal first trimester serum leptin demonstrates a significant negative association with neonatal weight in preeclamptic pregnancies and to a lesser extent in normotensive pregnancies. A possible leptin's involvement in pathophysiological adaptations that define the foetal growth potential can be supported.

Paradoxical Increase in Maternal Plasma Leptin Levels in Food-Restricted Gestation: Contribution by Placental and Adipose Tissue

Maternal food restriction (FR) during pregnancy results in decreased body weight with increased plasma leptin. To address this paradox, we investigated the effects of FR during pregnancy on growth and leptin levels in maternal, placental, and fetal sites. From embryonic day E10, control pregnant rats received ad libitum (AdLib) food, whereas study rats were 50% FR. At gestational ages, E16 and E20, the alterations in maternal body composition, retroperitoneal versus subcutaneous adipose leptin expression, and plasma leptin levels were studied. Furthermore, these changes were related to non-pregnant (NP) status and placental/fetal growth and leptin levels. As compared to NP, both FR and AdLib dams showed a progressive increase in body and lean body mass. However, total body fat was reduced in FR dams but remained unchanged in AdLib dams. Furthermore, plasma leptin levels in FR dams were markedly increased at E20 unlike AdLib dams, which showed moderate increments at E16 and E20. Additionally, FR dams showed significantly decreased leptin expression in subcutaneous and notably unaltered levels in retroperitoneal adipose tissue, suggesting an alternate source of elevated maternal plasma leptin. More importantly, the FR dams had reduced placental weights with paradoxical increased leptin expression at both gestations. Thus, increased plasma leptin levels at E20 in maternal FR pregnancies may be explained, in part, by upregulation of placental leptin. Despite maternal and placental hyperleptinemia during FR pregnancies, the growth-restricted FR fetus had reduced leptin levels. These findings have important implications for pregnancy outcome and fetal growth.

The Relationship between Maternal Plasma Leptin Levels and Fetal Growth Restriction

Leptin is a satiety hormone secreted from the adipose tissue and human placenta. We previously demonstrated that severe preeclampsia up-regulated leptin mRNA expression in the placenta and elevated maternal plasma leptin concentrations. Preeclampsia is frequently related to generation of small for gestational age (SGA) infant especially in cases with severe preeclampsia. However, it is still controversial whether the increase in maternal plasma leptin levels is associated with fetal growth restriction without complication of preeclampsia. Therefore, the aim of the present study was to explore the relationship between maternal plasma leptin levels and fetal growth in non-preeclamptic (n = 98) and preeclamptic (n = 40) women. In non-preeclamptic pregnant women, plasma leptin levels in SGA group (n = 11) were significantly higher than those in appropriate for gestational age (AGA) group (n = 87, P<0.05). In pregnant women with preeclampsia, likewise, plasma leptin levels in SGA group (n = 15) were significantly higher than those in AGA group (n = 25, P<0.05). In multiple linear regression analysis, maternal BMI, mean arterial blood pressure and Delta SD of neonatal body weight were significant factors for determining maternal plasma leptin levels in all population studied. Maternal BMI and Delta SD of neonatal body weight showed positive correlation with maternal plasma leptin levels when analysis was performed in non-preeclamptic subjects alone. In conclusion, maternal plasma leptin levels reflect, at least partly, deterioration in fetal growth.

Characterization of changes in leptin and leptin receptors in a rat model of preeclampsia

The purpose of this study was to determine the influence of reduced uteroplacental perfusion pressure on plasma leptin and placental leptin receptor expression in rats that develop hypertension in the third trimester of pregnancy. The ovarian arteries and abdominal aortae of pregnant Sprague-Dawley rats (n=9) were constricted surgically on day 14 of gestation and were matched with sham controls. Systolic blood pressure and weight were measured biweekly. Maternal plasma leptin levels, placental leptin receptor abundance, fetal number, fetal weight, and placental weight were determined. Reductions in perfusion pressure induced a significant decrease in maternal plasma leptin. Maternal systolic blood pressure and leptin receptor protein abundance was increased in the experimental group. Litter size and fetal and placental weight were significantly decreased in response to reduced perfusion pressure. Reduced uteroplacental perfusion pressure reduces litter size, fetal and placental weights, and maternal plasma leptin levels and increases placental expression of leptin receptors.

Fetal and maternal plasma leptin levels during the second half of normal pregnancies and those with Down syndrome

Fetal and maternal plasma leptin levels during the second half of normal pregnancies and those with Down syndrome

Fetal and maternal plasma leptin levels during the second half of normal pregnancies and those with Down syndrome

Objective: To assess the correlation of fetal and maternal plasma leptin concentrations during the second half of uncomplicated, euploid pregnancies and to compare these values with those obtainedfrom pregnancies with Down syndrome.Methods: Paired maternal venous and fetal umbilical blood samples were obtained during cordocentesis in 36 uncomplicated, euploid pregnancies and nine pregnancieswith Down syndrome fetuses. Concentrations of leptin were measured by sensitive radioimmunoassay. Results: Among pregnancies with euploid fetuses, there was significant correlation between both fetal andmaternal leptin levels and gestational age (r = 0.464, p = 0.005 and r = 0.629, p < 0.001, respectively). Fetal plasma leptin concentrations also correlated with maternal levels(r = 0.485, p = 0.003), but fetal levels were significantly lower than maternal values (mean 2.12 ± 0.44 ng/ml vs. 17.79 ± 5.48 ng/ml, respectively; p < 0.001). Downsyndrome fetuses had significantly lower fetal plasma leptin levels than gestational age-matched control euploid fetuses (0.72 + 0.54 ng/ml vs. 2.12 + 0.44 ng/ml; p < 0.002). However, there wasno difference in maternal leptin concentrations between euploid and Down syndrome pregnancies.Conclusion: In euploid pregnancies, fetal leptin levels were significantly lower than the correspondingmaternal values but increased across gestation. Down syndrome was associated with significantly lower fetal leptin levels.

Role of Leptin in Pregnancy—A Review

Leptin is an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. In rodents, it also modulates glucose metabolism by increasing insulin sensitivity. We previously reported that leptin is produced by human placental trophoblasts. We also revealed that leptin gene expression in the placenta was augmented in severe pre-eclampsia, and suggested that placental hypoxia may play a role in this augmentation. Maternal plasma leptin levels correlated well with mean blood pressure, but not with body mass index. Plasma leptin levels in pre-eclamptic women with IUGR were higher than those without IUGR (P< 0.05).We further examined the effects of hyperleptinemia on the course of pregnancy by using transgenic mice (Tg) overexpressing leptin. In pregnant Tg mice, food intake was significantly less than non-Tg, and the fetal body weights were reduced to approximately 70 per cent of those of non-Tg.Resistin is a novel adipocyte–derived hormone that decreases insulin sensitivity and increases plasma glucose concentration, thus contributing the development of obesity-related type II diabetes mellitus. We recently found that resistin gene is expressed in the human placenta as well as adipose tissue. In this review, possible roles of placental leptin and resistin are discussed.

Possible role of placental leptin in pregnancy: a review.

Leptin was initially identified as an adipocyte-derived hormone that decreases food intake and body weight via its receptor in the hypothalamus. Subsequent animal studies revealed various physiologic functions of leptin. Leptin plays an essential role in reproduction by regulating gonadotropin-releasing hormone secretion from the hypothalamus. It also modulates glucose metabolism by increasing insulin sensitivity and activates the sympathetic nervous system. In humans, leptin is also produced by placental trophoblasts and is secreted into both the maternal and fetal circulation. Leptin production in the placenta is increased in pregnancies complicated with several pathologic conditions. Leptin gene expression in the placenta is augmented in severe preeclampsia, and maternal plasma leptin levels in severe preeclampsia are significantly higher than those in normotensive pregnant women. Leptin production in the placenta is also increased in diabetic pregnancy with insulin treatment. Furthermore, leptin is proposed to play a functional role in implantation by virtue of its stimulatory effect on matrix metalloproteinase expression in cytotrophoblast. Dysregulation of leptin metabolism and/or function in the placenta may be implicated in the pathogenesis of various disorders during pregnancy, such as recurrent miscarriage, gestational diabetes, intrauterine growth retardation, and preeclampsia. In this review, possible roles of placental leptin are discussed.

Preeclampsia disrupts the normal physiology of leptin.

This study was designed to examine the leptin levels of preeclamptic women and their offspring, to compare them with those of normal pregnant women and to search for a correlation between maternal and fetal plasma leptin levels and their anthropometric characteristics. Twenty-one preeclamptic women and their babies were enrolled into the study. Control group consisted of 21 normal pregnant women and their babies, whose birth weights, gestational ages, and genders match with those of babies born to preeclamptic women. Median maternal leptin concentrations of the preeclamptic group (15.3 ng/mL) were significantly higher ( p = 0.03) than the control group (10.4 ng/mL). However, fetal plasma leptin concentrations were not different ( p = 0.06) between the two groups. Fetal plasma leptin levels were correlated with birth weight, length, body mass index, gestational age, and fetal hematocrit levels in the control group. However, no correlation between leptin levels and these parameters was found in the preeclamptic group. Therefore, preeclampsia may be thought to disrupt normal leptin physiology.

555 Fetal and maternal plasma leptin levels in the second and third trimesters of normal and down syndrome pregnancies

555 Fetal and maternal plasma leptin levels in the second and third trimesters of normal and down syndrome pregnancies

Physiological and pathological regulation of feto/placento/maternal leptin expression

There is clear evidence of placental leptin production, as shown recently in trophoblast cultures and by dual in vitro placenta perfusion (median production of 225 pg/min per g of tissue; 98.4% released into the maternal and 1.6% into the fetal circulation). However, the physiological impact for the mother and the fetus is unclear. The classical role of leptin is to provide information about energy stores to the central nervous system, and to reduce appetite if the energy stores are full. In pregnancy, maternal plasma leptin concentrations are elevated, and lack the well established correlation with body fat energy stores that is observed in non-pregnant women, indicating an alternative function for leptin during pregnancy and fetal development. Maternal and fetal plasma leptin levels are dysregulated in pathological conditions such as gestational diabetes, pre-eclampsia and intra-uterine growth retardation, representing an effect or a cause of disturbances in the feto/placento/maternal unit.

Alterations of maternal and fetal leptin concentrations in hypertensive disorders of pregnancy

Objectives: To investigate whether hypertensive disorders of pregnancy alter the maternal and fetal leptin levels. Methods: Fifty primigravidas between 28 and 34 weeks of gestation were divided into three groups: group A consisted of 17 normal pregnant women with a mean gestational age of 31 weeks, group B consisted of 15 women with gestational hypertension without proteinuria with a mean gestational age of 30 weeks and group C consisted of 18 pre-eclamptic women with a mean gestational age of 31 weeks. Results: The pre-eclamptics had significantly higher serum leptin levels than those in normal pregnancies ( p<0.001) but no difference was noted between normal and gestational hypertensive pregnancies. Pre-eclamptic women had significantly higher umbilical vein leptin levels (4.68±1.66 ng/ml) compared to normal pregnancies (1.92±0.71 ng/ml) and those with gestational hypertension (2.47±0.81 ng/ml). Conclusions: Pre-eclampsia is associated with an increase in maternal plasma leptin levels and fetal of leptin production increases in gestational hypertension and even more in pre-eclampsia.

Physiological and pathological regulation of feto/placento/maternal leptin expression.

There is clear evidence of placental leptin production, as shown recently in trophoblast cultures and by dual in vitro placenta perfusion (median production of 225 pg/min per g of tissue; 98.4% released into the maternal and 1.6% into the fetal circulation). However, the physiological impact for the mother and the fetus is unclear. The classical role of leptin is to provide information about energy stores to the central nervous system, and to reduce appetite if the energy stores are full. In pregnancy, maternal plasma leptin concentrations are elevated, and lack the well established correlation with body fat energy stores that is observed in non-pregnant women, indicating an alternative function for leptin during pregnancy and fetal development. Maternal and fetal plasma leptin levels are dysregulated in pathological conditions such as gestational diabetes, pre-eclampsia and intra-uterine growth retardation, representing an effect or a cause of disturbances in the feto/placento/maternal unit.