High‐fat diet before and during pregnancy causes marked up‐regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice

Abstract

Maternal overweight and obesity in pregnancy often result in fetal overgrowth, which increases the risk for the baby to develop metabolic syndrome later in life. However, the mechanisms underlying fetal overgrowth are not established. We developed a mouse model and hypothesized that a maternal high-fat (HF) diet causes up-regulation of placental nutrient transport, resulting in fetal overgrowth. C57BL/6J female mice were fed a control (11% energy from fat) or HF (32% energy from fat) diet for 8 wk before mating and throughout gestation and were studied at embryonic day 18.5. The HF diet increased maternal adiposity, as assessed by fat pad weight, and circulating maternal leptin, decreased serum adiponectin concentrations, and caused a marked increase in fetal growth (+43%). The HF diet also increased transplacental transport of glucose (5-fold) and neutral amino acids (10-fold) in vivo. In microvillous plasma membranes (MVMs) isolated from placentas of HF-fed animals, protein expression of glucose transporter 1 (GLUT1) was increased 5-fold, and protein expression of sodium-coupled neutral amino acid transporter (SNAT) 2 was elevated 9-fold. In contrast, MVM protein expression of GLUT 3 or SNAT4 was unaltered. These data suggest that up-regulation of specific placental nutrient transporter isoforms constitute a mechanism linking maternal high-fat diet and obesity to fetal overgrowth.

Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth

“…1 A and B). Similar to our previous report (21), maternal obesity increased transplacental transport of MeG by 3.8-fold (Fig. 1A) and MeAIB by fivefold (Fig.…”

“…At E18.5, a subgroup of fasted dams was used for measurements of maternal-fetal transfer of the radiolabeled isotopes MeAIB (PerkinElmer) and MeG (PerkinElmer), as previously reported (21). The time point (3 min) for ending the experiments was chosen based on pilot experiments terminating at 1.5, 3.0, and 4.5 min to ensure maternal-to-fetal transport of radiolabeled substrates was in the linear phase (Fig.…”

Saturated fat-rich diet increases fetal lipids and modulates LPL and leptin receptor expression in rat placentas

“…Additionally, mothers fed with the saturated fat-rich diet showed larger litters than the control ones. In total, more and heavier fetuses and placentas contribute to the increase in maternal weight gain, as seen by others (Jones et al 2009). Conversely, other experimental models fed with high-fat diets have shown a decrease in fetal weight, and a diminished placental efficiency, calculated by a fetal-to-placental weight ratio (Niculescu & Lupu 2009, Hayes et al 2012.…”

Perinatal exercise improves glucose homeostasis in adult offspring

“…A growing number of studies have been designed to provide evidence for the negative impact of DOHaD, using mice, rats, and sheep as animal models (11,12,31,38). Many of these studies are directed at malnutrition through protein restriction or physical stressors that produce similar effects (8,11,34,44,45), but more recent studies are elucidating the metabolic effects of high-fat diet consumption during pregnancy on offspring (22,38,44,48).It has been known since Hippocrates and Galen that physical activity is an important component of a healthy lifestyle (33). However, knowledge about the contributions of maternal exercise during pregnancy and the long-term consequences on offspring is minimal.…”