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Journal of Lipid Research, Vol. 46, 1491-1501, July 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Evidence for multiple complementary pathways for efficient cholesterol absorption in mice

Jahangir Iqbal and M. Mahmood Hussain¹

Department of Anatomy and Cell Biology, and Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY

Published, JLR Papers in Press, April 16, 2005. DOI 10.1194/jlr.M500023-JLR200

¹ To whom correspondence should be addressed. e-mail: Mahmood.hussain{at}downstate.edu

Apolipoprotein B (apoB)-dependent and apoB-independent pathways for cholesterol transport have been described in cultured cells. Here, we show that the apoB-independent pathway involves apoA-I-containing high density lipoproteins (HDLs). Cholesterol secretion by the HDLs, but not by the apoB pathway, was significantly reduced in primary enterocytes isolated from chow- and cholesterol-fed apoA-I^–/– mice. These enterocytes were capable of cholesterol efflux when apoA-I was provided extracellularly. In apoA-I^–/– mice, the absorption of a bolus of cholesterol was similar in control and apoA-I^–/– mice fed chow or high-cholesterol diet. However, short-term studies revealed that cholesterol absorption was occurring over longer lengths of the intestine, and cholesterol but not triglyceride transport to the plasma and liver in chow- and cholesterol-fed apoA-I^–/– mice was significantly reduced.

These studies indicate that in apoA-I deficiency, there is a delay in cholesterol absorption, but cholesterol is eventually absorbed because of the compensatory apoB pathway. Nonetheless, long-term studies involving multiple feedings showed significant reduction in cholesterol absorption after 4 days. We propose that multiple compensatory mechanisms ensure efficient cholesterol absorption in mice.

Abbreviations: ABCA1, ATP binding cassette protein A1; apoB, apolipoprotein B; HDL, high density lipoprotein; OA, oleic acid; TC, taurocholate

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