Ezetimibe Promotes Brush Border Membrane-to-Lumen Cholesterol Efflux in the Small Intestine
Fig 9
Brush border membrane as a major platform for cholesterol bidirectional flux.
A, Balance out of cholesterol translocation in the brush border membrane (BBM). The BBM is focused (the circle in the upper panel); the gray square indicates lipid bilayer, or microvillus. T, total input cholesterol incorporated into the BBM from the apical side. Cholesterol (T) diffuses into the BBM via the pathway (a). x, the amount of cholesterol transferred to endosomes for further processing via the pathway (b) and considered to be transferred eventually to the circulation, which of the following processes were not identified in this presentation. T—x, estimated amount of cholesterol effluxed into the lumen via the pathway (c). Thus, ‘x’ and ‘T—x’ should be inversely correlated. B, An illustration of the hypothesized bidirectional intestinal cholesterol flux system. Cholesterol diffuses into the BBM (pathway d; Fig 6); NPC1L1 mediates cholesterol movement from the BBM to the endosomal processing [e; Chang T-Y and Chang C. (2008, Ref. 24)]; Cholesterol that diffuses into the BBM can be caught by ABCG5/G8 in cholesterol-rich microdomains (f). ABCG5/G8 promotes elimination of sterols from the BBM when required or the sterols become in excess (g; Fig 6). Collectively, the BBM provides a buffering space for the bidirectional flux of cholesterol. C, A proposed route for TICE. Endogenous cholesterol circulates into the BBM (pathway, h). Ezetimibe prevents internalization of the cholesterol from the BBM (e) (Ref.24). The cholesterol in the BBM diffusively exits to the lumen or is pumped out by ABCG5/G8 (d and g).