Decreased hepatic uptake of cholesterol and retinol in the dimethylnitrosamine rat model of cirrhosis.

The fenestrated endothelium of the liver sinusoids forms a sieve between the circulation and hepatocytes. Fenestrae selectively permit the entrance of relatively small chylomicron remnants into the space of Disse to contact hepatocyte receptors, but obstruct the passage of the larger parent chylomicrons. Much of dietary cholesterol and most of retinol are transported as esters in the core of chylomicrons. In the dimethyl nitrosamine rat model of cirrhosis, we have described a rapid reduction in size and number of fenestrae well before the onset of cirrhosis. Concurrent with this decreased porosity is a decreased trapping of radio-labelled dietary cholesterol and retinol by these livers. We postulate that the less porous "liver sieve" hinders the hepatic uptake of chylomicron remnants, with consequent disturbance of cholesterol and retinol metabolism.