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 (ETAR) but not B (ETBR) density in the arteries. Furthermore, ETAR antagonism but not ETBR 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.