Submitted on January 20, 2005
Revised on March 18, 2005
Accepted on April 6, 2005
Evidence for multiple complementary pathways for efficient cholesterol absorption in mice
Jahangir Iqbal and M. Mahmood Hussain
Department of Anatomy and Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203
Corresponding Author: mhussain{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 apolipoprotein AI (apoAI)-containing high-density lipoproteins. Cholesterol secretion by the high-density lipoproteins, but not by the apoB, pathway was significantly reduced in primary enterocytes isolated from chow and cholesterol fed apoAI-/- mice. These enterocytes were capable of cholesterol efflux when apoAI was provided extracellularly. In apoAI-/- mice, the absorption of a bolus of cholesterol was similar in control and apoAI-/- 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 apoAI-/- mice was significantly reduced. These studies indicate that, in apoAI 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.
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