Maternal high-fat diet programs cerebrovascular remodeling in adult rat offspring

Abstract

Maternal environmental factors such as diet have consequences on later health of the offspring. We found that maternal high-fat diet (HFD) exposure renders adult offspring brain more susceptible to ischemic injury. The present study was further to investigate whether HFD consumption during rat pregnancy and lactation influences the cerebral vasculature in adult male offspring. Besides the endothelial damage observed in the transmission electron microscopy, the MCAs of offspring from fat-fed dams fed with control diet (HFD/C) also displayed increased wall thickness and media/lumen ratio, suggesting that cerebrovascular hypertrophy or hyperplasia occurs. Moreover, smaller lumen diameter and elevated myogenic tone of the MCAs over a range of intralumenal pressures indicate inward cerebrovascular remodeling in HFD/C rats, with a concomitant increase in vessel stiffness. More importantly, both wire and pressure myography demonstrated that maternal HFD intake also enhanced the MCAs contractility to ET-1, accompanied by increases in ET types A receptor (ETR) but not B (ETR) density in the arteries. Furthermore, ETR antagonism but not ETR antagonism restored maternal HFD-induced cerebrovascular dysfunction in adult offspring. Taken together, maternal diet can substantially influence adult offspring cerebrovascular health, through remodeling of both structure and function, at least partially in an ET-1 manner.

Maternal high-fat diet in mice induces cerebrovascular, microglial and long-term behavioural alterations in offspring

“…This remodelling was associated with increased blood vessel leakiness, measured by IgG extravasation, in the hippocampus of aged female offspring exposed to HFD throughout life 11 . Another investigation focused on remodelling of the middle cerebral artery showed that mHFD causes arterial wall thickening together with increased blood pressure in adult rat offspring 12 . Here, we reveal that mHFD leads to increased blood vessel density and branching (i.e., hypervascularization) accompanied by increased microglial proximity to vessels across the cerebral cortex but not the hippocampus, of adolescent offspring in both sexes.…”

“…However, the effects of mHFD on the offspring’s cerebrovascular health are still understudied. So far, it has been demonstrated that maternal obesity disturbs development of the blood-brain barrier in neonate rodent offspring 10 as well as leads to an increased vascular permeability in the hypothalamus of foetal, neonatal 10 and adult 11 , 12 rodent offspring. Even though neurovascular alterations are hypothesised as a main mechanism linking maternal immune activation to the onset of neurodevelopmental and neuropsychiatric disorders 9 , the effects of mHFD on the neurovascular system of brain regions involved in these disorders have remained elusive.…”

Pre- and Post-natal High Fat Feeding Differentially Affects the Structure and Integrity of the Neurovascular Unit of 16-Month Old Male and Female Mice

“…As discussed above, whether this is due to post-natal adaptations during brain maturation or insensitivity of the current methods to detect small or selective changes in BBB permeability remains unknown. Endothelial denudation and thickening of the middle cerebral artery has been reported in 6-month old rat offspring of obese mothers (Lin et al, 2018) and neonatal and adult HF/C offspring display larger infarct volumes and poorer functional deficits after stroke compared to C/C rats (Lin et al, 2016; Teo et al, 2017). We have previously reported that vessel morphology and thickness and GFAP expression were altered in the hippocampus of 5-month old HF/C male mice compared to C/C offspring (Hawkes et al, 2015).…”

Maternal High-Fat Diet Alters the Characteristics of Astrocytes and Worsens the Outcome of Stroke in Rat Offspring, Which Improves After FGF21 Administration

“…There is growing evidence that maternal high-fat diet (MHFD) can cause health problems in adult offspring, such as an increased susceptibility to ischemic stroke, which is a leading cause of death and disability ( Bejot et al, 2007 ). Lin et al (2016) , Lin et al (2018) found that MHFD could greatly affect adult cerebrovascular health by regulating central brain-derived neurotrophic factor expression and HPA axis, as well as through ET-1 manner in remodeling of both structure and function. Although these articles explain some of it, the underlying mechanism is still unclear.…”