Apolipoprotein A-I deficiency does not affect biliary lipid secretion and gallstone formation in mice.
OBJECTIVE
Apolipoprotein A-I (apo A-I) is the main protein component of plasma high-density lipoproteins (HDL) and a key determinant of HDL cholesterol levels and metabolism. The relevance of HDL in controlling the traffic of cholesterol from plasma into bile has been partially addressed. The aim of this study was to evaluate the role of apo A-I expression in controlling the secretion of biliary lipids as well as the risk of gallstone disease in vivo.


METHODS
We evaluated biliary lipid secretion and bile acid homeostasis in mice deficient for apo A-I compared with wild-type animals when fed with low- or high-cholesterol diets. In addition, we assessed the importance of murine apoA-I expression for gallstone formation after feeding a lithogenic diet.


RESULTS
Bile acid pool size and faecal excretion were within the normal range in chow- and cholesterol-fed apo A-I knockout (KO) mice. Basal biliary cholesterol secretion was comparable and increased similarly in both murine strains after cholesterol feeding. Lithogenic diet-fed apo A-I KO mice exhibited an impaired hypercholesterolaemic response owing to a lower increase in cholesterol levels transported in large lipoproteins. However, the lack of apo A-I expression did not affect biliary cholesterol precipitation or gallstone formation in lithogenic diet-fed mice.


CONCLUSIONS
These findings indicate that biliary lipid secretion, bile acid metabolism and gallstone formation are independent of apo A-I expression and plasma HDL cholesterol levels in mice.
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica, Santiago, Chile.
Ludwig
L
Amigo
Verónica
V
Quiñones
Andrea
A
Leiva
Dolores
D
Busso
Silvana
S
Zanlungo
Flavio
F
Nervi
Attilio
A
Rigotti
D000818:Animals; D016632:Apolipoprotein A-I / Q000172:deficiency* / Q000235:genetics; D001647:Bile Acids and Salts / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood*; D004036:Diet, Atherogenic; D005243:Feces / Q000737:chemistry; D042882:Gallstones / Q000503:physiopathology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000302:isolation & purification
D016632:Apolipoprotein A-I; D001647:Bile Acids and Salts; D008076:Cholesterol, HDL; D012333:RNA, Messenger