Abstract
Compelling experimental and clinical evidence supports a role for maternal obesity in offspring health. Adult children of obese mothers are at greater risk of obesity, diabetes, coronary heart disease and stroke. These offspring may also be at greater risk of age-related neurodegenerative diseases for which mid-life obesity is a risk factor. Rodent diet-induced obesity models have shown that high fat (HF) diet consumption damages the integrity of the blood–brain barrier (BBB) in the adult brain. However, there is currently little information about the effect of chronic HF feeding on the BBB of aged animals. Moreover, the long-term consequences of maternal obesity on the cerebrovasculature of aged offspring are not known. This study determined the impact of pre- and post-natal HF diet on the structure and integrity of cerebral blood vessels in aged male and female mice. Female C57Bl/6 mice were fed either a 10% fat control (C) or 45% HF diet before mating and during gestation and lactation. At weaning, male and female offspring were fed the C or HF diet until sacrifice at 16-months of age. Both dams and offspring fed the HF diet weighed significantly more than mice fed the C diet. Post-natal HF diet exposure increased hippocampal BBB leakiness in female offspring, in association with loss of astrocyte endfoot coverage of arteries. Markers of tight junctions, pericytes or smooth muscle cells were not altered by pre- or post-natal HF diet. Male offspring born to HF-fed mothers showed decreased parenchymal GFAP expression compared to offspring of mothers fed C diet, while microglial and macrophage markers were higher in the same female diet group. In addition, female offspring exposed to the HF diet for their entire lifespan showed more significant changes in vessel structure, BBB permeability and inflammation compared to male animals. These results suggest that the long-term impact of prenatal HF diet on the integrity of cerebral blood vessels differs between male and female offspring depending on the post-natal diet. This may have implications for the prevention and management of age- and obesity-related cerebrovascular diseases that differentially affect men and women.
Highlights
Rates of obesity have risen consistently over the past three decades (Ng et al, 2014) in association with increasingly sedentary lifestyles and consumption of diets that are high in saturated fat (Corella et al, 2011; Phillips et al, 2012)
The purpose of this study was to examine the impact of diet-induced maternal obesity on the structure and integrity of the neurovascular unit (NVU) and blood–brain barrier (BBB) in aged offspring in the presence or absence of chronic high fat (HF) feeding
We found that post-natal exposure to a HF diet resulted in increased leakiness of the BBB in the hippocampus of female offspring in association with loss of astrocyte endfoot coverage of hippocampal vessels
Summary
Rates of obesity have risen consistently over the past three decades (Ng et al, 2014) in association with increasingly sedentary lifestyles and consumption of diets that are high in saturated fat (Corella et al, 2011; Phillips et al, 2012). Global obesity of women aged 20 years and older is currently estimated to be around 30%, with prevalence close to or over 60% in some countries (Ng et al, 2014). There is a significant body of clinical and experimental evidence supporting an influence of maternal obesity on the health of adult offspring, including higher body-mass index (Hochner et al, 2012; Eriksson et al, 2015) and increased risk of coronary heart disease, diabetes, stroke, asthma and premature death (Reynolds et al, 2013; Parlee and MacDougald, 2014; Godfrey et al, 2017). Few studies have examined the impact of maternal obesity on offspring health beyond middle age
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
