Evidence for multiple complementary pathways for efficient cholesterol absorption in mice

J Lipid Res. 2005 Jul;46(7):1491-501. doi: 10.1194/jlr.M500023-JLR200. Epub 2005 Apr 16.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Absorption
  • Animals
  • Apolipoprotein A-I / deficiency
  • Apolipoprotein A-I / physiology*
  • Apolipoproteins B / physiology*
  • Caco-2 Cells
  • Cholesterol / metabolism*
  • Cholesterol, HDL / metabolism
  • Enterocytes / metabolism
  • Humans
  • Intestine, Small / anatomy & histology
  • Intestine, Small / metabolism
  • Lipoproteins, HDL / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout

Substances

  • Apolipoprotein A-I
  • Apolipoproteins B
  • Cholesterol, HDL
  • Lipoproteins, HDL
  • Cholesterol