Cholestyramine

C57BL/6 (male, 8 weeks old)^[1]

2%

dietary supplementation; ad libitum; 4 weeks

Showed no significant difference in body weight relative to control at any weekly time point over 4 weeks.
Robustly induced apical sodium-dependent bile acid transporter (Asbt) expression relative to control.
Significantly reduced ileal bile acid binding protein (Ibabp) and fibroblast growth factor 15 (Fgf15) expression relative to control.
Significantly increased expression of intestinal cholesterol synthesis genes 3-hydroxy-3-methylglutaryl-CoA synthase 1 (Hmgcs1) and 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr), as well as scavenger receptor class b, member 1 (Scarb1) and low density lipoprotein receptor (Ldlr) relative to control.
Induced cholesterol 7α-hydroxylase (Cyp7a1) expression 8-fold relative to control.
Increased sterol 12α-hydroxylase (Cyp8b1) expression relative to control.
Decreased oxysterol 7α-hydroxylase (Cyp7b1) expression relative to control.
Significantly increased expression of hepatic cholesterol synthesis genes Hmgcs1 and Hmgcr, as well as sterol regulatory element binding protein 1c (Srebf1c) and its lipogenic target genes acetyl CoA carboxylase 1 (Acc1), fatty acid synthase (Fasn), and stearoyl CoA desaturase (Scd1) relative to control.
Reduced serum bile acid levels relative to control.
Reduced serum triglyceride levels by 56% relative to control.
Reduced serum non-esterified fatty acid levels relative to control.
Showed no change in serum cholesterol, alanine aminotransferase (ALT), or aspartate aminotransferase (AST) levels relative to control.
Increased fecal bile acid excretion relative to control.
Increased total fecal lipid excretion relative to control.
Increased fecal non-esterified fatty acid excretion relative to control.
Showed no change in fecal cholesterol excretion relative to control.

C57BL/6 (male, 8 weeks old)^[1]

2% (cholestyramine); 250 mg/kg (GSPE)

dietary supplementation; ad libitum; 4 weeks (cholestyramine); p.o.; single dose (GSPE)

Robustly induced Asbt expression relative to control.
Significantly reduced Ibabp and Fgf15 expression relative to control.
Significantly increased expression of intestinal cholesterol synthesis genes Hmgcs1 and Hmgcr, as well as Acat2, Mttp, Scarb1, and Ldlr relative to control.
Induced Cyp7a1 expression nearly 13-fold relative to control.
Increased Cyp8b1 and sterol 27-hydroxylase (Cyp27a1) expression relative to control.
Showed no change in Cyp7b1 expression relative to control.
Attenuated the cholestyramine-induced increases in hepatic Hmgcs1, Hmgcr, Srebf1c, Acc1, Fasn, and Scd1 expression relative to cholestyramine alone.
Reduced serum bile acid levels to a greater extent than cholestyramine alone relative to control.
Reduced serum triglyceride levels by 66.7% relative to control (a 25% additional decrease compared to cholestyramine alone).
Reduced serum non-esterified fatty acid levels relative to control.
Showed no change in serum cholesterol, ALT, or AST levels relative to control.
Increased fecal bile acid excretion relative to control.
Increased total fecal lipid excretion relative to control.
Increased fecal non-esterified fatty acid excretion relative to control.
Showed no change in fecal cholesterol excretion relative to control.

C57BL/6J mice^[2]

2% (w/w)

p.o.; daily; 14 days

Decreased intestinal cholesterol absorption by 24%.
Increased fecal bile acid excretion several fold.
Increased fecal neutral sterol excretion at 0-4 h, 4-24 h, and 24-48 h.
Increased overall macrophage-to-feces RCT by 2.2-fold (4-24 h) and 3.6-fold (24-48 h).
Increased fecal tracer excretion within bile acids by 3.9-fold (4-24 h) and 3.2-fold (24-48 h).
Increased fecal tracer excretion within neutral sterols at 4-24 h and 24-48 h.
Did not change baseline plasma free or total cholesterol or triglyceride levels.
Caused a decrease in plasma free cholesterol levels at 4 h and an increase at 24 h and 48 h when combined with a single dose of rHDL (100 mg/kg apoA-I-POPC).
Showed no additive effect on RCT when combined with rHDL.