Submitted on January 21, 2009
Revised on March 12, 2009
Accepted on March 12, 2009
ABCA1 plays no role in the centripetal movement of cholesterol from peripheral tissues to the liver and intestine in the mouse
Chonglun Xie, Stephen D. Turley, and John M. Dietschy
Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-8887
Corresponding Author: john.dietschy{at}utsouthwestern.edu
Every cell in the body largely synthesizes the sterol it needs for turnover of plasma membrane cholesterol. This study uses the mouse to explore the role of ABCA1 in the movement of this cholesterol from the peripheral organs to the endocrine glands for hormone synthesis and liver for excretion. The sterol pool in all peripheral organs was constant and equaled 2218 and 2269 mg/kg, respectively, in abca1+/+ and abca1-/- mice. Flux of cholesterol from these tissues equaled the rate of synthesis plus the rate of LDL-C uptake and was 49.9 mg/day/kg in control animals and 62.0 mg/day/kg in abca1-/- mice. In the abca1+/+ animals, this amount of cholesterol moved from HDL into the liver for excretion. In the abca1-/- mice, the cholesterol from the periphery also reached the liver but did not utilize HDL. Fecal excretion of cholesterol was just as high in abac1-/- mice (198 mg/day/kg) as in the abac1+/+ animals (163 mg/day/kg) although the abac1-/- mice excreted relatively more neutral than acidic sterols. This study established that ABCA1 plays essentially no role in the turnover of cholesterol in peripheral organs or in the centripetal movement of this sterol to the endocrine glands, liver and intestinal tract for excretion.