EFFECTS OF DIETARY-CHOLESTEROL ON HEPATIC PRODUCTION OF LIPIDS AND LIPOPROTEINS IN ISOLATED HAMSTER LIVER

The effect of 2-week 2% cholesterol vs, chow feeding on regulation of hepatic lipoprotein, lipids and apoprotein (Apo), and biliary lipids p roduction was evaluated by the isolated perfused hamster liver model, Cholesterol feeding did not change very-low-density lipoprotein (VLDL) , low-density lipoprotein (LDL), and high-density lipoprotein (HDL) pa rticle size but significantly increased the hepatic production of VLDL -cholesterol fourfold, VLDL-triglyceride two and one-half-fold but not phospholipid in VLDL. It also increased LDL-cholesterol fourfold but not triglyceride or phospholipid in LDL, whereas Lipids in HDL remaine d unchanged. Gradient sodium dodecyl sulfate-polyacrylamide gel electr ophesis (SDS-PAGE) and Western blot analysis (density of apoprotein/de nsity of albumin/g liver) indicated that cholesterol feeding enhanced Apo B tenfold, Apo A-I fivefold but not Apo E in VLDL, Apo E and Apo B did mot change in LDL. Apo E but not Apo A-I increased (threefold) in HDL by cholesterol feeding, Cholesterol feeding decreased bile salt s ecretion 28% but increased cholesterol secretion 118% in bile, whereas phospholipid and bile volume remained unchanged, Increased Apo A-I in VLDL suggested that Apo A-I is involved in enhanced hepatic export of cholesterol and triglyceride. Different patterns of lipid and Apos in VLDL and LDL after cholesterol feeding also suggested separate VLDL a nd LDL export mechanisms, Elevated Apo E but not lipids in HDL after c holesterol feeding suggests that hepatic HDL may function as a carrier of newly synthesized hepatic Apo E into the circulation for transfer to other lipoproteins (chylomicron [CM], CM(r)) to facilitate hepatic cholesterol uptake and clearance.