Apolipoprotein A-I deficiency does not affect biliary lipid secretion and gallstone formation in mice.

Abstract

BACKGROUND/AIMS:

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.

• Authors: Ludwig Amigo, Verónica Quiñones, Andrea Leiva, Dolores Busso, Silvana Zanlungo, Flavio Nervi, Attilio Rigotti
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 31 Issue 2 Pg. 263-71 (Feb 2011) ISSN: 1478-3231 [Electronic] United States
• PMID: 21134113 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2010 John Wiley & Sons A/S.

Chemical References

• Apolipoprotein A-I
• Bile Acids and Salts
• Cholesterol, HDL
• RNA, Messenger

Topics

• Animals
• Apolipoprotein A-I (deficiency, genetics)
• Bile Acids and Salts (metabolism)
• Cholesterol, HDL (blood)
• Diet, Atherogenic
• Feces (chemistry)
• Gallstones (physiopathology)
• Mice
• Mice, Knockout
• RNA, Messenger (isolation & purification)