Maternal nitrate supplementation improves offspring cardiometabolic outcomes in obese pregnancies

Obesity during pregnancy is associated with excess adiposity and metabolic abnormalities in offspring due to fetal programming. Although the impact of dietary nitrate on cardiometabolic health has been established, it is unknown if maternal dietary nitrate intake would exhibit similar benefits to offspring. This study assessed cardiometabolic outcomes in offspring of Sprague-Dawley rats fed a high fat diet (HFD) with or without inorganic nitrate.

Eight-week-old female rats (n = 11) were randomized to 10% normal fat diet (NFD) or 45% HFD. Upon confirmation of obesity, some HFD rats (n = 4) were transitioned to HFD with 40 mg inorganic nitrate (HFDN). NFD (n = 4), HFD (n = 3), and HFDN (n = 4) maintained their respective diets, yet all weanling pups were transitioned to NFD at post-natal day 21 (P21). Body composition was assessed by bioimpedance spectroscopy along with assessment of body weight (BW), and abdominal circumference as well as brown adipose tissue (BAT) and white adipose tissue (WAT) mass. Serum nitrate, cardiometabolic biomarkers (glucose, insulin, total cholesterol, HDL-cholesterol, and triglycerides, along with serum redox status), blood pressure, and protein levels of F₁Fo ATP synthase c-subunit in BAT were assessed.

Prior to mating, HFD and HFDN females exhibited significantly greater BW and fat mass (p = 0.01) compared to the NFD group. Serum nitrate was significantly higher in HFDN dams, yet there were no significant differences in maternal cardiometabolic biomarkers between groups. At P21, BW was significantly lower in pups reared by NFD and HFDN dams compared to those reared by HFD dams (p = 0.044, p = 0.027, respectively). Abdominal circumference and glucose were significantly lower in HFDN pups compared to NFD (p = 0.004, p = 0.003, respectively) and HFD pups (p = 0.011, p = 0.006, respectively). At P65, abdominal circumference was lower in HFDN pups compared to NFD and HFD pups, albeit non-significantly. HFDN pups also exhibited significantly lower triglycerides compared to HFD pups (p = 0.004). Additionally, pups born to HFD-fed dams exhibited significantly decreased protein levels of F₁Fo ATP synthase c-subunit in pups at both P21 and P65, yet nitrate supplementation significantly reversed the effects of the HFD at P21 (p = 0.046) and P65 (p = 0.0056).

Results suggest periconceptional and prenatal nitrate supplementation may beneficially impact cardiometabolic outcomes of offspring born from an overweight or obese pregnancies including body weight, abdominal circumference, glucose dynamics, and lipid profiles. Further, results suggest that maternal intake of dietary nitrate impacts cellular responses during fetal development, thus regulating energy metabolism of offspring. .