Targeted disruption of the murine cholecystokinin-1 receptor promotes intestinal cholesterol absorption and susceptibility to cholesterol cholelithiasis
J. Clin. Invest. David Q.-H. Wang, et al. 114:521 doi:10.1172/JCI16801 [
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Figure 1Relative lipid compositions of bile specimens from CCK-1R
–/– and WT mice. Relative lipid compositions (mol per 100 mol) are plotted on partial condensed phase diagrams according to the approximate total lipid concentrations of the bile samples (
A, 10.0 g/dl for gallbladder bile;
B, 2.0 g/dl for hepatic bile; see Table
1). The one-phase micellar zone (at bottom) is enclosed by a solid curved line, and two solid and two dashed lines divide the phase diagram into regions a–e with different crystallization sequences (see ref.
24). (
A) Lipid compositions of pooled gallbladder bile specimens (
n = 20 per group) from the CCK-1R
–/– (circle) and WT mice (square) fed the lithogenic diet for 12 weeks are located in a central three-phase area where, at equilibrium, bile samples are composed of cholesterol-saturated mixed micelles, solid cholesterol crystals, and liquid crystals, as observed by microscopy. (
B) Analogous regions of the condensed phase diagram exhibit the same physical states at equilibrium as those in the phase diagram shown in
A; however, with decreases in total lipid concentration all crystallization pathways are shifted to the left and the micellar zone becomes smaller. These alterations generate a new condensed phase diagram with an enlarged region e. Lipid compositions of individual hepatic bile specimens (
n = 6 per group) from both WT (squares) and CCK-1R
–/– mice (circles) locate in region e, where, at equilibrium, the bile samples are composed of liquid crystals and saturated micelles, but no solid cholesterol monohydrate crystals are present.