Predictive Adaptive Responses to Maternal High-Fat Diet Prevent Endothelial Dysfunction but Not Hypertension in Adult Rat Offspring

Background—Population-based studies suggest that fetal adaptive responses to maternal dietary imbalance confer survival benefit when the postnatal diet remains suboptimal but increase susceptibility to cardiovascular disease when postnatal nutrition is improved. We have investigated “predictive adaptive” responses in a rodent model in which adult offspring of fat-fed dams develop characteristics of the metabolic syndrome. Methods and Results—Sprague-Dawley rats were fed a fat-rich diet or normal chow throughout pregnancy and weaning. Vascular endothelial function and blood pressure were determined in 180-day-old offspring of fat-fed dams raised on standard chow (FC) or on the fat-rich diet (FF) and in offspring of chow-fed dams raised on chow (CON). Small mesenteric artery endothelium-dependent dilation to acetylcholine was impaired in male and female FC (by ANOVA, P<0.001 versus CON) but similar to CON in FF (P=NS). Blood glucose was lower in FF versus FC. Heart rate was reduced in male FC versus CON (P<0.05) but not in FF. Plasma triglyceride concentrations were reduced in male FF compared with CON (P<0.05). Blood pressure was raised in female FC (systolic, 132.5±3.0 mm Hg versus CON, 119.0±3.8 mm Hg, P<0.05; diastolic, 91.2±1.7 mm Hg versus CON, 81.1±1.4 mm Hg, P<0.05) and in female FF (systolic, 132.5±4.2 mm Hg versus CON, P<0.05; diastolic, 91.0±1.9 mm Hg versus CON, P<0.05). Blood pressure was similar to CON in male FC and FF. Conclusions—Predictive adaptive responses prevent endothelial dysfunction and reduced heart rate in offspring of fat-fed dams if offspring are raised on the same diet but do not prevent development of raised blood pressure.