Maternal high-fat diet impacts endothelial function in nonhuman primate offspring
L Fan1, S R Lindsley, S M Comstock
1Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR 97006, USA.
Insights
Maternal high-fat diet (HFD) exposure during pregnancy and early life impairs offspring endothelial function and cardiovascular health. Diet intervention after weaning can partially reverse these negative effects.
Area of Science:
- Cardiovascular Science
- Developmental Biology
- Nutritional Science
Background:
- Maternal under-nutrition's link to offspring cardiovascular disease (CVD) is known.
- The impact of maternal over-nutrition on offspring cardiovascular health is unclear.
- This study investigates maternal high-fat/calorie diet (HFD) effects on offspring endothelial function.
Purpose of the Study:
- To determine the impact of maternal HFD exposure on offspring endothelial function.
- To assess cardiovascular and metabolic changes in offspring exposed to maternal HFD.
- To evaluate the role of early programming and postweaning diet on offspring cardiovascular health.
Main Methods:
- Nonhuman primates were exposed to control (CTR) or HFD during pregnancy and early postnatal periods.
- Offspring were maintained on CTR or HFD, or switched diets postweaning.
- Vascular function, plasma insulin, glucose levels, and arterial morphology were assessed at 13 months of age.
Main Results:
- Maternal HFD offspring (HFD/HFD) showed increased insulin and impaired vasorelaxation in the abdominal aorta.
- HFD/HFD offspring exhibited thicker intima walls and abnormal vascular morphology with elevated inflammation markers.
- Diet-switched offspring showed modest vascular damage, suggesting partial reversibility.
Conclusions:
- Maternal HFD exposure during critical developmental periods significantly impairs offspring endothelial function.
- Both early developmental programming and postweaning diet influence offspring cardiovascular abnormalities.
- Dietary intervention postweaning can partially ameliorate the negative cardiovascular consequences of maternal HFD exposure.
Objective:
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.
Methods:
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.
Results:
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.
Conclusion:
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.

