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

Abstract

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.

Influence of high fat diet and resveratrol supplementation on placental fatty acid uptake in the Japanese macaque

“…HFD offspring of this model display anxiety-like behavior [33] and increased vascular reactivity [16, 34], consistent with exposure to low levels of n-3 LCPUFA during fetal development [35, 36]. Though we found that resveratrol supplementation improves the ability of the HFD placenta to take up DHA, fetal n-3 LCPUFA levels in circulation remain low [27].…”

“…Japanese macaques fed a diet composed of 35% fat, comparable to a typical western-style diet, before and during pregnancy have offspring born with fatty liver who develop obesity and vascular dysfunction in later life [15, 16]. Characteristics of these pregnancies include maternal insulin resistance, decreased uterine blood flow, decreased plasma LCPUFA levels, high placental triglycerides and placental inflammation [17], mimicking complications observed in pregnancies of obese women [18–20], and possibly altering placental nutrient handling.…”

Developmental programming by maternal obesity in 2015: Outcomes, mechanisms, and potential interventions

“…Given that obesity itself increases the risk of heart disease, cardiac dysfunction may be exaggerated in high-fat-fed offspring exposed to maternal obesity. Indeed, the combination of maternal HFD and post-weaning exposure to HFD culminates in reduced vasorelaxation in both mice and nonhuman primates (Fan et al, 2013;Torrens et al, 2012), with increased oxidative stress in the femoral arteries of adult male offspring (Torrens et al, 2012).…”

Understanding the control of ingestive behavior in primates

“…The research conducted with nonhuman primate models thus far suggests that the consequences of maternal HFD consumption and/or obesity during pregnancy generally have an adverse impact on a number of peripheral metabolic systems in both macaque (Fan et al, 2013; Grant et al, 2011; McCurdy et al, 2009; Suter et al, 2012a; Suter et al, 2012b) and baboon offspring (Farley et al, 2009; Maloyan et al, 2013). While the approach used to study diet-induced effects on central neuropeptide regulation and metabolic systems is quite informative, what is understudied is whether the maternal feeding phenotype is transmitted to the offspring.…”