Maternal high-fat diet impacts endothelial function in nonhuman primate offspring

• Published in: International Journal of Obesity Vol. 37; no. 2; pp. 254 - 262
• Main Authors: FAN, L, LINDSLEY, S. R, COMSTOCK, S. M, TAKAHASHI, D. L, EVANS, A. E, HE, G.-W, THORNBURG, K. L, GROVE, K. L
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.02.2013
• Subjects: Abdomen; Animals; Animals, Newborn; Biological and medical sciences; Calories; Cardiovascular diseases; Carotid Intima-Media Thickness; Complications and side effects; Coronary vessels; Demographic aspects; Diabetes; Diet; Diet, High-Fat - adverse effects; Disease; Disease Models, Animal; Endothelium; Endothelium, Vascular - pathology; Fasting - blood; Female; Fetal Growth Retardation - metabolism; Fetal Growth Retardation - physiopathology; Gene Expression Regulation, Developmental; General aspects; Health aspects; Insulin resistance; Ketogenic diet; Liver - metabolism; Macaca; Male; Maternal Nutritional Physiological Phenomena; Maternal-Fetal Exchange; Medical sciences; Metabolic diseases; Metabolic disorders; Neurosciences; Nutrition research; Obesity; Obesity - blood; Obesity - complications; Obesity - pathology; Obesity in children; Original; Overnutrition - blood; Overnutrition - complications; Placental Insufficiency - pathology; Pregnancy; Prenatal Exposure Delayed Effects - blood; Prenatal Exposure Delayed Effects - pathology; Primates; Prognosis; Real-Time Polymerase Chain Reaction; Research centers; Risk factors; Weaning; United States; Oregon; United States > US; Human; Obesity; Nutrition; Nutrition disorder; Programming; Metabolic diseases; In utero; Feeding; Endothelium; over-nutrition; Progeny; Vertebrata; intrauterine; juvenile offspring; Mammalia; Mother; Diet; Uterus; Female genital system; Fat; Primates; Child; Nutritional status
• ISSN: 0307-0565; 1476-5497
• DOI: 10.1038/ijo.2012.42

The link between maternal under-nutrition and cardiovascular disease (CVD) in the offspring later in life is well recognized, but the impact of maternal over-nutrition on the offspring's cardiovascular function and subsequent risk for CVD later in life remains unclear. Here, we investigated the impact of maternal exposure to a high-fat/calorie diet (HFD) during pregnancy and early postnatal period on endothelial function of the offspring in a nonhuman primate model. Offspring, naturally born to either a control (CTR) diet (14% fat calories) or a HFD (36% fat calories) consumption dam, were breast-fed until weaning at about 8 months of age. After weaning, the offspring were either maintained on the same diet (CTR/CTR, HFD/HFD), or underwent a diet switch (CTR/HFD, HFD/CTR). Blood samples and arterial tissues were collected at necropsy when the animals were about 13 months of age. HFD/HFD juveniles displayed an increased plasma insulin level and glucose-stimulated insulin secretion in comparison with CTR/CTR. In abdominal aorta, but not the renal artery, acetylcholine-induced vasorelaxation was decreased remarkably for HFD/HFD juveniles compared with CTR/CTR. HFD/HFD animals also showed a thicker intima wall and an abnormal vascular-morphology, concurrent with elevated expression levels of several markers related to vascular inflammation and fibrinolytic function. Diet-switching animals (HFD/CTR and CTR/HFD) displayed modest damage on the abdominal vessel. Our data indicate that maternal HFD exposure impairs offspring's endothelial function. Both early programming events and postweaning diet contribute to the abnormalities that could be reversed partially by diet intervention.