Maternal choline supplementation mitigates premature foetal weight gain induced by an obesogenic diet, potentially linked to increased amniotic fluid leptin levels in rats

Abstract

Placental leptin may impact foetal development. Maternal overnutrition has been linked to increased plasma leptin levels and adverse effects on offspring, whereas choline, an essential nutrient for foetal development, has shown promise in mitigating some negative impacts of maternal obesity. Here, we investigate whether a maternal obesogenic diet alters foetal growth and leptin levels in the foetal stomach, amniotic fluid (AF), and placenta in late gestation and explore the potential modulating effects of maternal choline supplementation. Female rats were fed a control (CD) or a western diet (WD) four weeks before mating and during gestation, half of them supplemented with choline (pregnancy days 11-17). Leptin levels (in foetal stomach, AF, and placenta) and leptin gene expression (in placenta) were assessed on gestation days 20 and 21. At day 20, maternal WD feeding resulted in greater leptin levels in foetal stomach, placenta, and AF. The increased AF leptin levels were associated with a premature increase in foetal weight in both sexes. Maternal choline supplementation partially prevented these alterations, but effects differed in CD dams, causing increased AF leptin levels and greater weight in male foetuses at day 20. Maternal choline supplementation effectively mitigates premature foetal overgrowth induced by an obesogenic diet, potentially linked to increased AF leptin levels. Further research is needed to explore the sex-specific effects.

Keywords: Choline; Foetal development; Leptin; Perinatal nutrition; Sex-dependent metabolic programming.

Figure 1

Foetal body weight (g) at gestational days 20 and 21, depending on maternal diet (standard chow (control) diet—CD—or western diet—WD) and maternal supplementation (vehicle or choline) of female (a) and male (b) foetuses. Data are mean ± SEM. Statistics: three-way (bottom box) and two-way (upper boxes) ANOVA with diet (WD), supplementation (Chol), and Day as factors. U-Mann Whitney test was used for single comparisons, with significant differences (p < 0.05) indicated by * (choline vs. vehicle), ^# (western vs. control diet), and ^↑ (day 21 vs. 20; with the % of change between both days). Mean size of litters is given at the bottom part of the figure.

Figure 2

Leptin levels in amniotic fluid (AF), gastric content (GC) (pg/mL), and stomach (pg/g tissue) at gestational days 20 and 21, depending on maternal diet (standard chow (control) diet—CD—or western diet—WD) and maternal supplementation (vehicle or choline) of female (a) and male (b) foetuses. Data are mean ± SEM. Statistics: three-way (bottom box) and two-way (upper boxes) ANOVA with diet (WD), supplementation (Chol), and Day as factors. U-Mann Whitney test was used for single comparisons, with significant differences (p < 0.05) indicated by * (choline vs. vehicle), ^# (western vs. control diet), and ^↑ (day 21 vs. 20; with the % of change between both days).

Figure 3

Placental leptin mRNA (% vs. control) and protein (pg/g tissue) at gestational days 20 and 21, depending on maternal diet (standard chow (control) diet—CD—or western diet—WD) and maternal supplementation (vehicle or choline) of female (a) and male (b) foetuses. Data are mean ± SEM. Statistics: three-way (bottom box) and two-way (upper boxes) ANOVA with diet (WD), supplementation (Chol), and Day as factors. U-Mann Whitney test was used for single comparisons, with significant differences (p < 0.05) indicated by * (choline vs. vehicle), ^# (western vs. control diet), and ^↑ (day 21 vs. 20 with the % of change between both days).

Figure 4

Correlation analysis between (a) gastric, stomach, and placental leptin levels and amniotic fluid (AF) leptin levels, and between (b) foetal body weight and AF at gestational days 20 and 21. In the case of gastric content and stomach, samples were pooled for leptin measurement (2–3 stomach samples per pool), and samples of the same pool shared the same value of leptin level for the correlation test. Statistics: lineal coefficient of determination (R²); Pearson correlation coefficient (and p-value) are given.