Impaired biliary cholesterol secretion and decreased gallstone formation in apolipoprotein E-deficient mice fed a high-cholesterol diet.
OBJECTIVE
Because apolipoprotein E (apoE) is a key cholesterol transport molecule involved in the hepatic uptake of chylomicron cholesterol, it may play a critical role in controlling bile cholesterol elimination and cholesterol gallstone formation induced by dietary cholesterol. To test this hypothesis, we studied biliary lipid secretion and gallstone formation in apoE-deficient mice fed cholesterol-rich diets.


METHODS
Bile lipid outputs and gallstone sequence events were analyzed in apoE-deficient mice fed a high-cholesterol diet or a lithogenic diet compared with control animals.


RESULTS
A high-cholesterol diet increased biliary cholesterol secretion and gallbladder bile cholesterol concentration in wild-type mice; the increase in bile cholesterol secretion was significantly attenuated in apoE-deficient mice. ApoE knockout mice fed a high-cholesterol lithogenic diet had a markedly lower frequency of gallbladder bile cholesterol crystal and gallstone formation than wild-type mice, which was most likely a result of the decreased cholesterol saturation index found in gallbladder bile of apoE-deficient mice.


CONCLUSIONS
These results show that apoE expression is an important factor for regulating both biliary secretion of diet-derived cholesterol as well as diet-induced cholesterol gallstone formation in mice.
Amigo
L
L
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
Quiñones
V
V
Mardones
P
P
Zanlungo
S
S
Miquel
J F
JF
Nervi
F
F
Rigotti
A
A
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000378:metabolism; D002769:Cholelithiasis / Q000209:etiology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D002791:Cholesterol, Dietary / Q000008:administration & dosage* / Q000494:pharmacology; D004032:Diet; D005704:Gallbladder / Q000378:metabolism; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics
D001057:Apolipoproteins E; D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D008074:Lipoproteins; C030104:lipoprotein cholesterol; D002784:Cholesterol