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L'apeline, un marqueur d'intérêt chez la femme enceinte obèse ?

Abstract : Obesity is a major public health problem and is constantly increasing. Obesity alters the adipokines’ secretion, such as apeline. Apeline is involved in various functions, such as energy metabolism regulating. During pregnancy, the apelinergic system seems to be crucial for fetal development. The apelinergic system in obese pregnant women has never been studied before. The aim of this thesis was to verify whether the apelinergic system is modified in case of obesity in pregnant women, first by an experimental approach on an obese and insulin-resistant mouse model and then by a translational approach to the human (OB-APE study). Material and methods : Murine model: 40 female mice were divided into 2 groups: Control (C, n = 20) and High Fat (HF, n = 20). After 10 weeks of diet, mice were mated. Samples were taken at E6.5, E12.5 and E18.5. Mice were sacrificed by decapitation at E18.5 and blood samples were collected. Fetuses and placentas were collected after cesarean section and weighed. Fasting blood glucose, insulinaemia, maternal and fetal apelinemia were measured. At E18.5, blood samples of fetuses were collected and placentas were frozen and stored at -80°C. Human model (OB-APE study) : Prospective and comparative study conducted in Jeanne de Flandre maternity (Lille, France) between May 2016 and July 2017. Patients were divided into 3 groups: group N (normal, n=30), group O (obese, n=30) and group ODG (obese with diabetes mellitus, n=30). The maternal plasma samples were obtained at 3 different times: at the end of pregnancy (35-40 weeks of gestation), at delivery and at day 2 in postpartum, as well as a neonatal umbilical cord sampling. Placental fragments were collected at delivery and colostrum was recovered on day 2 in postpartum. The measures of apelin concentrations in plasma and colostrum were performed by ELISA. The placental expression of apelin and APJ was studied by quantitative RT-PCR. Placental secretion was studied in a standard nutrient medium (DMEM) as well as in presence of insulin (50nM) or angiotensin II (AT2, 1nM). Results: Murine model: After 3 months of diet, HF mice were obese and intolerant to carbohydrates. There was no significant difference in fasted apelinemia between non-pregnant T and HF mice. The placentas of HF mice were heavier than controls (P=0.006). There was an increase in apelinemia at E12.5 in the 2 groups (P<0.05), higher in the group HF (4.89 ± 1.18 ng/mL, vs 2.44 ± 0.42 ng/mL, P<0.001). In obese mice, there was an increase in insulin-resistance at the end of pregnancy compared to the group T (P<0.05). The placental expression of apelin and APJ was increased in obese mice. Human model (OB-APE study) : Maternal apelinemia was decreased in the O and ODG groups in comparison with the N group at the 3 times of the study. Neonatal apelinemia was also decreased in these groups. The apelin concentrations in colostrum were higher in the groups O and ODG than in the group N (P=0.007 and P=0.05 respectively). Ex-vivo, placental secretion of apelin was decreased in the groups O and ODG compared to the group N. The addition of insulin in the medium led to an increase in apelin secretion, whereas the addition of AT2 led to a diminution of this secretion. Placental expression of APJ mRNA was greater in placentas of obese women than in normal (N) patients [...]
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Submitted on : Saturday, September 21, 2019 - 1:01:27 AM
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Sandy Hanssens-Gilbert. L'apeline, un marqueur d'intérêt chez la femme enceinte obèse ?. Médecine humaine et pathologie. Université du Droit et de la Santé - Lille II, 2017. Français. ⟨NNT : 2017LIL2S030⟩. ⟨tel-02293623⟩



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