The worldwide prevalence of childhood obesity has increased dramatically in the past several decades.1
Numerous epidemiological studies have documented a close association between early-onset obesity and the risk for developing cardiovascular diseases (CVDs) in adulthood.2, 3, 4
Maternal health and diet during pregnancy and the early postnatal period is now known to be the major contributing factor to the manifestation of metabolic disorders in obese children.5, 6, 7
A clear association has been established in humans between nutritional restriction and placental insufficiency during pregnancy with the connection to CVD in their offspring later in life. These effects have been confirmed in sheep models.8, 9, 10, 11, 12
In addition, there are data in rodent models,13, 14, 15
demonstrating that maternal over-nutrition can impair cardiovascular function in obese offspring as adults; however, it was not determined if the endothelial dysfunction occurred before the onset of obesity. Our current study aims to determine the relative impact of exposure to a high-fat/calorie diet (HFD) during the prenatal and/or postnatal period on endothelial function in juvenile nonhuman primate (NHP) offspring.
We have established a maternal HFD NHP model,16
where monkeys are maintained on a HFD before and throughout pregnancy and lactation. Using this model, our ongoing studies16, 17, 18, 19, 20, 21
demonstrated that consumption of a HFD during pregnancy leads to broad developmental health issues in the offspring, independent of maternal obesity and insulin resistance. These studies have found that the fetal offspring demonstrated restricted fetal growth, placental insufficiency accompanied by a decrease in placental blood flow volume, increased release of cytokines, dyslipidemia and an increased deposition of fat in the liver. Moreover, after birth, the HFD offspring displayed catch-up growth, increased fat mass and persistent fatty liver. These are all hallmarks for an increased risk of CVD. However, few studies to date have been conducted on the effects of maternal HFD intake on the cardiovascular system of the offspring, especially on an NHP model.
High-fat dietary intake is a major risk factor for the development of obesity. Obesity is closely associated with a number of established cardiovascular risk factors, including diabetes mellitus, insulin resistance, dyslipidemia and hypertension, which are cumulatively damaging to endothelial function.22, 23, 24
The structural and functional integrity of the vascular endothelium has a crucial role in cardiovascular homeostasis. Abnormal endothelial function is a well-recognized precursor of atherosclerotic disease. Under normal circumstances, the vascular endothelium releases various vasodilator and vasoconstrictor substances that regulate local vascular tone to ensure adequate blood flow, as well as regulate platelet aggregation and leukocyte adhesion to the endothelium. All of these effectively counteract the onset of atherosclerosis.25
On the contrary, in a state of insulin resistance, such as obesity and diabetes, endothelium-dependent vasodilator response, the most useful measurement of endothelium function,26
is depressed.27, 28, 29, 30
Based on the evidence that endothelial dysfunction is the central pathogenic feature of metabolic-disease-associated cardiovascular disorders,30, 31, 32
and based on our previous findings, we hypothesized that maternal HFD consumption during pregnancy and the perinatal period would impair the endothelial function of the offspring. In order to test our hypothesis, we collected abdominal aorta and renal arteries from 13-month-old NHP juvenile animals to test endothelial function, using multiple techniques. Apart from understanding the programming effects on the CVD risk in the juvenile offspring as a consequence of maternal obesity, this study also aimed to determine the contribution of dietary vs early programming events to endothelial dysfunction. In addition, these studies investigate the possible beneficial contribution of dietary intervention in juvenile animals, after the potential early programming events have occurred.