An in vivo evaluation in man of the transfer of esterified cholesterol between lipoproteins and into the liver and bile.

The metabolism of the esterified cholesterol fractions of HDL and LDL has been studied in vivo in man with regard to their ability to serve as precursors (after intrahepatic hydrolysis) for bile acid synthesis and biliary cholesterol secretion. Information was also obtained on the exchange of cholesterol esters between the lipoprotein classes. Fasting subjects were intravenously administered autologous HDL (or LDL) labeled with esterified [3H]cholesterol and free [3H]- and [14C]cholesterol. Following the administration of the labeled lipoproteins, bile and blood were collected at frequent intervals. In each experiment the observed 3H/14C ratios in bile acids, biliary cholesterol, lipoprotein free cholesterol and red blood cell cholesterol were similar and markedly divergent from the lipoprotein esterified cholesterol 3H/14C ratios. Following the administration of labeled HDL, the 3H/14C ratios observed in the esterified cholesterol fractions of VLDL and LDL closely resembled the ratios in HDL indicating that VLDL and LDL received esterified cholesterol by direct transfer from HDL. Following the administration of labeled LDL, the 3H/14C ratios in HDL esterified cholesterol were midway between the ratio in LDL esterified cholesterol and plasma free cholesterol, indicating that HDL esterified cholesterol is derived from more than one source. These sources could be LDL esterified cholesterol and esters formed de novo from plasma free cholesterol. A precursor-product relationship was found between the specific activities of lipoprotein free cholesterol and the bile steroids. Assuming direct entry of lipoprotein free and esterified cholesterol (after hydrolysis) into the bile acid and biliary cholesterol precursor pools, it was calculated that less than 20% of these biliary steroids could be derived from HDL esterified cholesterol. The results support the view that lipoprotein free cholesterol is the major source of bile acids in man. Also, the results suggest that in vivo esterified cholesterol fractions of VLDL and LDL originate from HDL, that some LDL ester is transferred back to HDL, and that the cholesterol liberated form hydrolyzed esters undergoes recirculation into the free cholesterol pool rather than excretion as biliary cholesterol or bile acids.