Combined perinatal and offspring high‐fat diet exaggerates body mass and adiposity but not blood pressure levels during pregnancy of these offspring
Authors: Spradley Frank T 
Published: June 2021

Although perinatal high‐fat diet (HFD) programs for obesity and hypertension in female offspring in rats, less is known about how perinatal HFD impacts the pregnancy of the offspring. Furthermore, it is unknown whether perinatal HFD mediates the reductions in placental growth factor (PlGF) found in obese pregnancies. PlGF is a vasoprotective factor that activates endothelial nitric oxide synthase (NOS3). Therefore, the hypothesis was tested that perinatal HFD promotes obesity and hypertension along with reductions in PlGF during pregnancy of the offspring. For this purpose, Wistar Hannover rat dams were maintained on normal‐fat diet (NFD; 13% kcal from fat, 0.1% NaCl) or HFD (39.7% kcal from fat, 0.12% NaCl) throughout gestation and lactation. There were no differences in the number offspring between NFD (11±2) or HFD (12±1) dams. At weaning, offspring were started on NFD (N=6–10), which resulted in the following groups, which were defined as Dam (D)‐NFD/Offspring (O)‐NFD or D‐HFD/O‐NFD. At ~12 weeks of age, body weight was similar between groups (D‐NFD/O‐NFD: 253±5 g vs. D‐HFD/O‐NFD: 274±10 g). These rats were used to generate timed pregnancies. By gestational day 19, maternal body weight (320±5 vs. 331±6 g), total body fat mass (EchoMRI: 50±2 vs. 50±3 g), isolated visceral fat (16±2 vs. 15±1 g), the plasma adipokine leptin (3.3±0.4 vs 4.5±0.7 ng/mL), plasma PlGF (10±2 vs. 15±2 pg/mL), and conscious mean arterial blood pressure (MAP: 110±3 vs 110±2 mmHg, measured by carotid catheter) were similar in D‐NFD/O‐NFD and D‐HFD/O‐NFD groups, respectively. However, Western blotting revealed that NOS3/B‐actin expression was greater (P<0.05) in mesenteric arteries from D‐HFD/O‐NFD (0.25±0.02 vs. 0.13±0.02 AU). As studies have reported that HFD promotes obesity and hypertension during pregnancy, we examined whether offspring from D‐HFD compared to D‐NFD have potentiated HFD‐induced obesity, reduced PlGF levels, and hypertension during pregnancy using groups defined as D‐NFD/O‐HFD or D‐HFD/O‐HFD. At ~12 weeks of age, before pregnancy, body weight was greater (P<0.05) in D‐HFD/O‐HFD over D‐NFD/O‐HFD (306±9 vs 264±5 g). On gestational day 19, body weight (388±14 vs 327±9 g), total body fat (86±6 vs 66±5 g), and visceral fat (28±2 vs. 21±2 g) were greater (P<0.05); PlGF (10±1 vs 15±2 pg/mL) was less (P<0.05); and leptin (5.2±0.6 vs 4.9±0.4 ng/mL) and MAP (119±3 vs 116±4 mmHg) were similar between D‐HFD/O‐HFD vs D‐NFD/O‐HFD groups, respectively. Mesenteric artery NOS3/B‐actin expression was non‐significantly lower in D‐HFD/O‐HFD (0.15±0.01 vs. 0.20±0.01 AU). When comparing all 4 offspring groups via two‐way ANOVA, D‐HFD/O‐HFD had augmented body weight, fat mass, and reductions in PlGF and NOS3 during pregnancy. Both D‐NFD/O‐HFD and D‐HFD/O‐HFD had similar elevations in MAP during pregnancy. There was no difference in average fetal or placental weights, respectively, between D‐NFD/O‐NFD (1.77±0.04, 0.43±0.02 g), D‐HFD/O‐NFD (1.81±0.06, 0.46±0.02 g), D‐NFD/O‐HFD (1.79±0.04, 0.41±0.01 g) and D‐HFD/O‐HFD (1.85±0.06, 0.46±0.03 g). In summary, combined perinatal and offspring HFD exaggerates body mass and adiposity but not blood pressure levels during pregnancy of these offspring.Support or Funding InformationNIH HL130577This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.