Targeting the LSEC to prevent age related disease

The fenestrations of the liver sinusoidal endothelium (LSEC) are a highly efficient ultrafiltration system that facilitate the transfer of plasma, solutes and small particulate substrates between the blood and hepatocytes.... [ view full abstract ]

The fenestrations of the liver sinusoidal endothelium (LSEC) are a highly efficient ultrafiltration system that facilitate the transfer of plasma, solutes and small particulate substrates between the blood and hepatocytes. However a hallmark of liver disease and old age is reduced fenestration diameter and/or frequency are diminished we have shown transfer across the LSEC is reduced, which we have previously shown to cause deficits in hepatic drug and lipoprotein metabolism. Recently we have shown that age-related defenestration also has a significant impact on hepatic insulin clearance leading to hyperinsulinemia, hepatic insulin resistance, impaired hepatic insulin signalling and deranged glucose homeostasis. Liver defenestration thus provides a new mechanism and a novel therapeutic target for age-related insulin resistance.