Efficient Hepatic Uptake of Chylomicron Remnant Cholesterol in Rats with a Portacaval Anastomosis

Abstract

Portacaval-shunted and sham-operated male rats, fed ad libitum and of similar weight, were studied 2-3 weeks after surgery. At this time serum cholesterol levels did not differ significantly between the two groups, whereas serum triacylglycerols and phospholipids were lower in the shunted group. These animals also showed an increased serum bile acid level and an increased serum estradiol to testosterone ratio. The metabolism of native chyle labeled with [3H]cholesterol and [14C]linoleic acid or of preformed chylomicron remnants with the same labeling was studied in the groups of rats. Ten minutes after intravenous injection of chylomicron remnants 10.6 +/- 0.5% (means +/- SEM, n = 8) of the injected [3H]cholesterol and 7.6 +/- 0.4% of the [14C]linoleic acid were found per 1 g liver in the portacaval-shunted rats; the corresponding figures in the sham-operated group (n = 8) were 6.4 +/- 0.4 and 4.9 +/- 0.3, respectively (p less than 0.001 for both 3H and 14C). Thus, despite a greater than 40% reduction of liver weight induced by the shunting procedure, the total liver uptake of chylomicron remnants was not significantly decreased. The uptake of chylomicron lipids per unit liver weight was normal in the atrophic livers of portacaval-shunted rats also when very large loads of chyle were administered.

The Clearance Rate of Chylomicron Retinyl Ester from Plasma Can Be Used to Distinguish Rats with Cirrhosis from Those with Portacaval Shunt

“…Although Cooper, Nutik and Chen (16) found steroid-induced LDL binding on only hepatocytes, we cannot rule out the possibility that the increment in I, in Eck fistula rats is due to the increase in extrahepatic clearance of the retinyl esters. The putative organ or tissue responsible for this possible extrahepatic clearance remains to be identified, although minor increment of remnant uptake by lung, kidney and spleen is known in Eck fistula rats (25). As shown in Table 3, the same concentration of plasma estrogen found in the shunt rats was observed in the cirrhotic rats, who had a low I,.…”

“…One hypothesis to explain this is that CC1,-treated rats sustain such extensive hepatocyte injury that they no longer respond to increases in plasma estrogen by up-regulating LDL receptor expression. Similarly efficient uptake of chylomicron remnants in Eck fistula rats is reported as per gram of liver tissue (25). Because lipoprotein lipase activities in adipose tissue and muscle seem not to be increased (25), the elevated I, is not mainly due to changes in lipoprotein lipase activities but to the enhanced uptake from the plasma.…”