Differential body weight, blood pressure and placental inflammatory responses to normal versus high-fat diet in melanocortin-4 receptor-deficient pregnant rats

Objectives:Although obesity increases the risk for hypertensive disorders of pregnancy, the mechanisms remain unclear. Neural melanocortin-4 receptor (MC4R) deficiency causes hyperphagia and obesity. Effects of MC4R deficiency on body weight, blood pressure (BP) and placental inflammatory responses to high-fat diet (HFD) are unknown. We tested two hypotheses: MC4R deficiency results in higher body weight, BP and placental inflammation under normal-fat diet (NFD) conditions and HFD exaggerates these responses in MC4R-deficient pregnant rats.Methods:MC4R(+/+) and MC4R(+/-) rats were maintained on NFD (13% kcal fat) or HFD (40% kcal fat) for approximate to 15 weeks, then measurements made on gestational day 19.Results:MC4R(+/-) pregnant rats had greater body mass and total body fat and visceral adipose tissue weights along with greater circulating total cholesterol (TC) and leptin levels than MC4R(+/+) rats regardless of diet. On NFD, circulating adiponectin levels were lower and placental TNF levels and BP (conscious with carotid catheter) were higher in these heavier rats. Circulating adiponectin levels were lower and placental TNF levels and BP were higher in MC4R(+/+) rats compared with NFD controls. These parameters were not affected by HFD in the already heavier and hypertensive MC4R(+/-) pregnant rats.Conclusion:Obesity in MC4R deficiency and HFD in MC4R(+/+) rats result in higher BP and placental inflammation during pregnancy. However, HFD did not exaggerate these responses in already obese MC4R(+/-) pregnant rats. These data suggest that obesity and HFD are independently related to hypertension and placental inflammation in pregnancy.