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Journal of Lipid Research, Vol. 50, 1316-1329, July 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

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. Dietschy¹

Department of Internal Medicine, University of Texas Southwestern Medical School, Dallas, TX 75390-9151

This work was supported by U.S. Public Health Service Grant R01 HL09610 (J.M.D. and S.D.T.) and by a grant from the Moss Heart Fund (J.M.D.).

Published, JLR Papers in Press, March 12, 2009.

¹ To whom correspondence should be addressed. e-mail: john.dietschy{at}utsouthwestern.edu

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 2,218 and 2,269 mg/kg, respectively, in abca1^+/+ and abca1^–/– mice. Flux of cholesterol from these tissues equaled the rate of synthesis plus the rate of LDL-cholesterol 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 use 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.

Supplementary key words ATP binding cassette transporter A1 • Tangier disease • low density lipoprotein transport • high density lipoprotein transport • cholesterol synthesis • cholesterol absorption • reverse cholesterol transport • steroid hormones

Abbreviations: apoAI, apolipoprotein AI; CETP, cholesteryl ester transfer protein; HDL-C, cholesterol carried in high density lipoprotein; LDL-C, cholesterol carried in low density lipoprotein; LDLR, low density lipoprotein receptor; NPC, Niemann-Pick type C

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