Maternal high fat diet reversal improves placental hemodynamics in a nonhuman primate model of diet-induced obesity

BACKGROUND: In a Japanese macaque model of diet-induced obesity, we have previously demonstrated that consumption of a high fat, ‘Western-style’ diet (WSD) is associated with placental dysfunction and adverse pregnancy outcomes, independent of an obese maternal phenotype. Specifically, we have reported decreased uterine placental blood flow and increased inflammation with maternal WSD consumption. We also previously investigated the use of a promising therapeutic intervention that mitigated the adverse placental effects of a WSD but had unexpected detrimental effects on fetal pancreatic development. Thus, the objective of the current study was to determine whether simple preconception diet reversal would improve placental function. METHODS: Female Japanese macaques were divided in to three groups: diet reversal animals (n=5) were switched from a chronic WSD (36% fat) to a low fat, control diet (14% fat) prior to conception and throughout pregnancy. The control (n=6) and WSD (n=6) cohorts were maintained on their respective diets throughout pregnancy. Maternal body weight and composition were regularly assessed and advanced non-invasive imaging was performed at mid-gestation (gestational day 90, G90 or 0.5 of gestation, where full term is G175), and G129, one day prior to C-section delivery at G130 (0.75 of gestation). Imaging studies comprised Doppler ultrasound (US), Contrast-Enhanced US (CEUS) and Dynamic-Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to assess uteroplacental hemodynamics and maternal-side placental perfusion. RESULTS: Dietary intervention resulted in significant maternal weight loss prior to pregnancy, and improved lean to fat mass ratio. By advanced imaging we demonstrated that a chronic WSD led to decreased blood flow velocity in the intervillous space, delayed blood flow transfer through the maternal spiral arteries and reduced total placental blood flow compared to control fed animals. Dietary reversal ameliorated these concerning derangements, restoring these hemodynamic parameters to control levels. CONCLUSION: Preconception dietary modification has beneficial effects on the maternal metabolic phenotype, and results in improved placental hemodynamics.