Simon-Pierre Noël

Secretion of Cholesterol-Rich Lipoproteins by Perfused Livers of Hypercholesterolemic Rats

Rats maintained on a high-fat diet supplemented with propylthiouracil develop a hypercholesterolemia, an increased serum level of apolipoprotein (apo) E, abnormal very low density lipoproteins (VLDL) and low density lipoproteins (LDL), and a fatty liver which contains cholesterol ester as its major lipid. The fatty liver secretes apoE into a recirculating perfusate at a significantly higher rate and produces cholesterol ester-rich, apoC-deficient VLDL with slower electrophoretic mobility than the triacylglycerol-rich VLDL produced by perfused normal livers. LDL, secreted in significant quantities by the perfused fatty liver, but not by the normal liver, is also cholesterol rich and contains apoE as well as apoB. The incorporation of [(3)H]leucine into apoVLDL and apoLDL secreted by the livers of the hypercholesterolemic animals and the apoVLDL secreted by the normal liver corresponds to the pattern visualized when the apoproteins are separated by polyacrylamide gel electrophoresis. Similar patterns are noted when non-recirculating perfusates are studied. These results indicate that the cholesterol ester-rich, apoC-deficient VLDL and the apoE-containing LDL found in the serum of hypercholesterolemic rats are not solely catabolic remnants of VLDL and chylomicrons but are secreted by the liver. Separation of the perfusate lipoproteins by agarose gel filtration revealed that most of the apoE secreted by the livers of hypercholesterolemic rats is found in the VLDL and LDL, whereas apoE secreted by the normal livers is distributed equally between VLDL, high density lipoproteins, and a low molecular weight fraction which corresponds to the virtually delipidated apoprotein. Thus the distribution of apoE among the lipoprotein fractions may be related to the total amount of cholesterol being transported in the circulation.

An in vitro model for the catabolism of rat chylomicrons

Summary An in vitro model for the study of the catabolism of chylomicrons is suggested and characterized. The model utilizes the ability of perfused rat hearts to hydrolyze triglycerides of chylomicrons obtained from rat thoracic ducts. The resulting remnants were re-isolated and perfused through rat livers where the remnant lipid and protein was rapidly removed. In contrast intact chylomicrons were taken up by perfused liver to a limited extent. The remnants produced by cardiac perfusion contained a decreased percent of triglycerides and apoproteins C-2 and C-3, with a relative increase primarily in diglycerides and, to a lesser extent, monoglycerides and cholesterol. Most of the 125I-labelled remnant protein lost during hepatic perfusion was recovered in the tissue. The model thus simulated many of the known characteristics of chylomicron catabolism in vivo .

Secretion of high density lipoprotein by the isolated perfused alcoholic rat liver

Chronic alcohol feeding of a low fat diet for 5 weeks led to a slightly raised though statistically non-significant high density liproprotein cholesterol/apoB containing lipoprotein cholesterol ratio in both the fasting rat serum as well as the secretory products of the isolated perfused liver.