Evidence for multiple complementary pathways for efficient cholesterol absorption in mice

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. - Iqbal, J., and M. M. Hussain. Evidence for multiple complementary pathways for efficient cholesterol absorption in mice.