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
Jahangir
J
Department of Anatomy and Cell Biology, and Pediatrics, SUNY Downstate Medical Center, Brooklyn, NY, USA.
Hussain
M Mahmood
MM
D000042:Absorption; D000818:Animals; D016632:Apolipoprotein A-I / Q000172:deficiency / Q000502:physiology*; D001055:Apolipoproteins B / Q000502:physiology*; D018938:Caco-2 Cells; D002784:Cholesterol / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000378:metabolism; D020895:Enterocytes / Q000378:metabolism; D006801:Humans; D007421:Intestine, Small / Q000033:anatomy & histology / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D002784:Cholesterol