Protein restriction during pregnancy affects maternal liver lipid metabolism and fetal brain lipid composition in the rat

Abstract

Suboptimal developmental environments program offspring to lifelong metabolic problems. The aim of this study was to determine the impact of protein restriction in pregnancy on maternal liver lipid metabolism at 19 days of gestation (dG) and its effect on fetal brain development. Control (C) and restricted (R) mothers were fed with isocaloric diets containing 20 and 10% of casein. At 19 dG, maternal blood and livers and fetal livers and brains were collected. Serum insulin and leptin levels were determinate in mothers. Maternal and fetal liver lipid and fetal brain lipid quantification were performed. Maternal liver and fetal brain fatty acids were quantified by gas chromatography. In mothers, liver desaturase and elongase mRNAs were measured by RT-PCR. Maternal body and liver weights were similar in both groups. However, fat body composition, including liver lipids, was lower in R mothers. A higher fasting insulin at 19 dG in the R group was observed (C = 0.2 +/- 0.04 vs. R = 0.9 +/- 0.16 ng/ml, P < 0.01) and was inversely related to early growth retardation. Serum leptin in R mothers was significantly higher than that observed in C rats (C = 5 +/- 0.1 vs. R = 7 +/- 0.7 ng/ml, P < 0.05). In addition, protein restriction significantly reduced gene expression in maternal liver of desaturases and elongases and the concentration of arachidonic (AA) and docosahexanoic (DHA) acids. In fetus from R mothers, a low body weight (C = 3 +/- 0.3 vs. R = 2 +/- 0.1 g, P < 0.05), as well as liver and brain lipids, including the content of DHA in the brain, was reduced. This study showed that protein restriction during pregnancy may negatively impact normal fetal brain development by changes in maternal lipid metabolism.

Fig. 1.

Maternal liver stearoyl-CoA desaturase-1 (SCD-1) relative abundance gene expression by real-time PCR assay (A) and %fatty acid (stearic and oleic) by gas chromatography (B) at 19 days of gestation (dG) of rats fed control (C; 20% protein) or restricted (R; 10% protein) diet during pregnancy. Means ± SE; n = 5. *P < 0.05 vs. C.

Fig. 2.

Maternal liver desaturases (A), elongase relative abundance gene expression by real time RT-PCR (B), and %fatty acid [arachidonic acid (AA) and docosahexaeonic acid (DHA)] by gas chromatography (C) at 19 dG of rats fed C (20% protein) or R (10% protein) diet during pregnancy. Means ± SE; n = 5. **P < 0.001; *P < 0.05 vs C. Δ5D and Δ6D, Δ5 and Δ6 desaturase; Elovl-2 and -5, elongase-2 and -5.

Fig. 3.

Northern blot analysis of Δ5D and Δ6D (A) and relative abundance or mRNA/ribosomal 28S of maternal liver (B) at 19 dG of rats fed C (20% protein) or R (10% protein) diet during pregnancy. Means ± SE; n = 4.

Fig. 4.

Maternal liver Δ5D gene expression as a function of serum insulin at 19 dG of rats fed C (20% protein) or R (10% protein) diet during pregnancy. Pearson correlation, P = 0.008 and r = −0.78.

Fig. 5.

Fetal brain weight (A), lipids (B; mg/100 mg), %DHA (C), and photograph at 19 dG (D) of rats fed C (20% protein) or R (10% protein) diet during pregnancy. Means ± SE (n = 6–7 litters/group). *P < 0.05 vs. C.

Fig. 6.

Fetal body weight as a function of maternal serum insulin at 19 dG. Pearson correlation, P = 0.002 and r = −0.78 (n = 6 mothers or litters).

Fig. 7.

Adaptative mechanisms proposed in the pregnant rat subjected to isocaloric protein restriction diet during pregnancy.