Relationship between Hepatic Cholesterol Synthesis and Biliary Cholesterol Secretion in Man: Hepatic Cholesterol Synthesis is not a Major Regulator of Biliary Lipid Secretion

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Abstract
1. To examine the role of newly synthesized cholesterol as a determinant of bile lipid secretion, both hepatic cholesterol synthesis (as judged by the activity of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, EC 1.1.1.34; HMGCoAR) and steady state biliary cholesterol output were measured in nine patients. 2. HMGCoAR levels varied four fold (9–40 pmol min−1 mg−1) and biliary cholesterol secretion 2–5-fold (0.60−1.15 μUmol h−1 kg−1) but there was no correlation between these two variables (r = 0.18; P>0.05) nor between biliary bile acid output and HMGCoAR activity (r = 0.34; P>0.05). 3. There was, however, a linear relationship between bile acid and phospholipid secretion (r = 0.77; Pr = 0.69; P<0.05). 4. These results suggest that HMGCoAR activity is not a major determinant of cholesterol secretion nor at these secretion rates is HMGCoAR activity related to bile acid return to the liver.