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 production 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) particle 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 remained unchanged. Gradient sodium dodecyl sulfate‐polyacrylamide gel electrophesis (SDS‐PAGE) and Western blot analysis (density of apoprotein/density 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 not change in LDL. Apo E but not Apo A‐I increased (threefold) in HDL by cholesterol feeding. Cholesterol feeding decreased bile salt secretion 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 and LDL export mechanisms. Elevated Apo E but not lipids in HDL after cholesterol 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], CMr) to facilitate hepatic cholesterol uptake and clearance.