Hepatobiliary cholesterol transport as not impaired in Abca1-null mice lacking HDL

The ABC transporter ABCA1 regulates HDL levels and is considered to control the first step of reverse cholesterol transport from the periphery to the liver. To test this concept, we studied the effect of ABCA1 deficiency on h epatic metabolism and hepatobiliary flux of cholesterol in mice. Hepatic li pid contents and biliary secretion rates were determined in Abca1(-/-), Abc a1(+/-), and Abca1(+/+) mice with a DBA background that were fed either sta ndard chow or a high-fat, high-cholesterol diet. Hepatic cholesterol and ph ospholipid contents in Abca1(-/-) mice were indistinguishable from those in Abca1(+/-) and Abca1(+/+) mice on both diets. In spite of the absence of H DL, biliary secretion rates of cholesterol, bile salts, and phospholipid we re unimpaired in Abca1(-/-) mice. Neither the hepatic expression levels of genes controlling key steps in cholesterol metabolism nor the contribution of de novo synthesis to biliary cholesterol and bile salts were affected by Abca genotype. Finally, fecal excretion of neutral and acidic sterols was similar in all groups. We conclude that plasma HDL levels and ABCA1 activit y do not control net cholesterol transport from the periphery via the liver into the bile, indicating that the importance of HDL in reverse cholestero l transport requires re-evaluation.