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

1] Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA [2] Cardiovascular Research Laboratory, Starr Academic Center, Providence Heart and Vascular Institute, Portland, OR, USA.
International journal of obesity (2005) (Impact Factor: 5). 03/2012; 37(2). DOI: 10.1038/ijo.2012.42
Source: PubMed


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.

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Available from: Diana L Takahashi, Jan 02, 2014
    • "In general, offspring experimental diets were applied at weaning through the end of the study period; based on the small number exceptions (Arentson-Lantz et al., 2014; Brenseke et al., 2015; Couvreur et al., 2011; Khanal et al., 2014; Llopis et al., 2014; Ong and Muhlhausler, 2014; Vido et al., 2014; Wallace et al., 2012), we observed no remarkable patterns with regard to the post-gestational timing of exposure to experimental offspring diets. Compared to a healthy offspring diet, a post-weaning Western-type offspring diet exacerbated the effects of the mother's obesity on weight gain or adiposity (Bayol et al., 2007; Chen et al., 2009; Ong and Muhlhausler, 2014; White et al., 2009), glucose/insulin regulation (Arentson-Lantz et al., 2014; Benkalfat et al., 2011; Chen et al., 2009; Flynn et al., 2013; Khanal et al., 2014; Li et al., 2013; Page et al., 2009; Rajia et al., 2010; Shalev et al., 2010; Srinivasan et al., 2006; Volpato et al., 2012), cardiovascular measures (Fan et al., 2013; Turdi et al., 2013), or fatty liver (Bouanane et al., 2010; Bruce et al., 2009; Hellgren et al., 2014; Li et al., 2013; Mouralidarane et al., 2013; Pruis et al., 2014; Zhang et al., 2013) in the offspring in most studies. For example, Chen and colleagues report that homeostatic model assessment of insulin resistance (HOMA-IR) was similar among rat offspring with high fat prenatal diet alone (0.46) compared to control prenatal and post-weaning diet (0.35); elevated among those with control prenatal and high fat post-weaning diet (0.62); and dramatically elevated among those with high fat control and post-weaning diet combined (1.15; p for interaction N 0.05) (Chen et al., 2009). "
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    ABSTRACT: Prenatal development is recognized as a critical period in the etiology of obesity and cardiometabolic disease. Potential strategies to reduce maternal obesity-induced risk later in life have been largely overlooked. In this paper, we first propose a conceptual framework for the role of public health and preventive medicine in mitigating the effects of fetal programming. Second, we review a small but growing body of research (through August 2015) that examines interactive effects of maternal obesity and two public health foci - diet and physical activity - in the offspring. Results of the review support the hypothesis that diet and physical activity after early life can attenuate disease susceptibility induced by maternal obesity, but human evidence is scant. Based on the review, we identify major gaps relevant for prevention research, such as characterizing the type and dose response of dietary and physical activity exposures that modify the adverse effects of maternal obesity in the offspring. Third, we discuss potential implications of interactions between maternal obesity and postnatal dietary and physical activity exposures for interventions to mitigate maternal obesity-induced risk among children. Our conceptual framework, evidence review, and future research directions offer a platform to develop, test, and implement fetal programming mitigation strategies for the current and future generations of children.
    No preview · Article · Nov 2015 · Preventive Medicine
    • "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). In summary, early life exposure to hyperleptinaemia as a consequence of maternal obesity may drive increased sympathetic tone leading to hypertension and accelerate the onset of cardiac hypertrophy and heart failure. "
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    ABSTRACT: Obesity in women of child-bearing age is a growing problem in developed and developing countries. Evidence from human studies indicates that maternal BMI correlates with offspring adiposity from an early age and predisposes to metabolic disease in later life. Thus the early life environment is an attractive target for intervention to improve public health. Animal models have been used to investigate the specific physiological outcomes and mechanisms of developmental programming that result from exposure to maternal obesity in utero. From this research, targeted intervention strategies can be designed. In this review we summarise recent progress in this field, with a focus on cardiometabolic disease and central control of appetite and behaviour. We highlight key factors that may mediate programming by maternal obesity, including leptin, insulin and ghrelin. Finally, we explore potential lifestyle and pharmacological interventions in humans and the current state of evidence from animal models. Copyright © 2015. Published by Elsevier Inc.
    No preview · Article · Jul 2015 · Hormones and Behavior
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    • "control diet) and 71% lower in their offspring [32]. 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]. "
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    ABSTRACT: INTRODUCTION: Adequate maternal supply and placental delivery of long chain polyunsaturated fatty acids (LCPUFA) is essential for normal fetal development. In humans, maternal obesity alters placental FA uptake, though the impact of diet remains uncertain. The fatty fetal liver observed in offspring of Japanese macaques fed a high fat diet (HFD) was prevented with resveratrol supplementation during pregnancy. We sought to determine the effect of HFD and resveratrol, a supplement with insulin-sensitizing properties, on placental LCPUFA uptake in this model. METHODS: J. macaques were fed control chow (15% fat, n = 5), HFD (35% fat, n = 10) or HFD containing 0.37% resveratrol (n = 5) prior to- and throughout pregnancy. At ∼130d gestation (term = 173d), placentas were collected by caesarean section. Fatty acid uptake studies using (14)C-labeled oleic acid, arachidonic acid (AA) and docosahexanoic acid (DHA) were performed in placental explants. RESULTS: Resveratrol supplementation increased placental uptake of DHA (P < 0.05), while HFD alone had no measurable effect. Resveratrol increased AMP-activated protein kinase activity and mRNA expression of the fatty acid transporters FATP-4, CD36 and FABPpm (P < 0.05). Placental DHA content was decreased in HFD dams; resveratrol had no effect on tissue fatty acid profiles. DISCUSSION: Maternal HFD did not significantly affect placental LCPUFA uptake. Furthermore, resveratrol stimulated placental DHA uptake capacity, AMPK activation and transporter expression. Placental handling of DHA is particularly sensitive to the dramatic alterations in the maternal metabolic phenotype and placental AMPK activity associated with resveratrol supplementation.
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