Impact of high cholesterol intake on tissue cholesterol content and lipid transfers to high-density lipoprotein.

OBJECTIVE

Esterified cholesterol is the storage form of cholesterol in the organism. High-density lipoprotein (HDL), where free cholesterol is transferred from other lipoproteins and tissues, is the main esterification site in plasma. The aim of this study was to investigate how high cholesterol intake changes free/esterified ratios of cholesterol in the plasma, aorta, liver and lipid transfers to HDL.

METHODS

Twenty male Golden Syrian hamsters fed 0.5% cholesterol for 15 wk and 19 controls without cholesterol feeding were sacrificed to determine serum lipids, transfer proteins (cholesteryl ester transfer protein and phospholipid transfer protein), and amount of free and esterified cholesterol in the aorta and liver. In vitro transfer of radioactive free and esterified cholesterol, phospholipids, and triacylglycerols to HDL was performed by incubating whole plasma with an artificial nanoemulsion used as a lipid donor and measuring radioactivity in the HDL fraction after chemical precipitation of non-HDL fractions and of the nanoemulsion.

RESULTS

Compared with controls, cholesterol-fed animals showed a 137% increase in non-HDL plasma fraction and a 61% increase in HDL (P < 0.001). The esterified/free cholesterol ratio in non-HDL and HDL fractions did not change. In the aorta, free cholesterol increased 55% and the esterified/free ratio (0.2) decreased. Cholesterol accumulation in the liver was several-fold greater and esterified/free increased (1.3). Cholesterol feeding pronouncedly increased the transfer of free and esterified cholesterol, phospholipids, and triacylglycerols to HDL and cholesteryl ester transfer protein and phospholipid transfer protein activities.

CONCLUSIONS

Free cholesterol is cytotoxic and less stable than esterified cholesterol, and the present data on how the organism responds to high cholesterol intake with respect to esterified/free ratios in the plasma, aorta, liver, and lipid transfers to HDL may have physiopathologic implications.