Western diet-induced endothelial glycocalyx remodeling is partially reversed by fasting

A Western diet (WD) that contains high fat and sugar content increases the risk of diabetes and diabetes-related vascular dysfunction. The endothelial glycocalyx is a gel-like structure bound to the vascular endothelium that is depleted in patients with diabetes, as well as in preclinical models of diabetes. Glycocalyx depletion is believed to initiate vascular dysfunction. However, early glycocalyx adaptations prior to diabetes remain uncertain, as we have shown that glycocalyx thickness and integrity are increased, rather than depleted, one week after initiating WD in mice. Despite greater glycocalyx properties, WD-fed mice still develop vascular dysfunction, suggesting that WD-induced glycocalyx remodeling may be a potential risk factor for diabetes-related vascular dysfunction. Therefore, we sought to determine the transient nature of WD-induced glycocalyx remodeling in response to a 6-hour fast as a minimally intensive intervention. Glycocalyx properties were examined in non-fasted and 6-hour fasted mice after one week of control or WD consumption. Increased glycocalyx thickness in WD mice was abolished by fasting, while glycocalyx thickness was unaffected by fasting in control mice. Glycocalyx integrity was greater in WD compared to control mice but was unaffected by fasting in NC and WD mice. We observed no meaningful differences in microcirculatory hemodynamics between groups. Collectively, WD-induced glycocalyx thickening was rapidly reversed by fasting, providing insight into the transient nature of glycocalyx remodeling in response to a 6-hour fast, suggesting that glycocalyx remodeling is one of the earliest and potentially modifiable vascular adaptations to WD, highlighting it as a potential target for future studies.