Format

Send to

Choose Destination
Gastroenterology. 2011 Oct;141(4):1404-11, 1411.e1-2. doi: 10.1053/j.gastro.2011.06.062. Epub 2011 Jul 2.

Hepatic overexpression of abcb11 promotes hypercholesterolemia and obesity in mice.

Author information

1
Division of Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.

Abstract

BACKGROUND & AIMS:

ABCB11 is a canalicular transport protein that controls the rate-limiting step in hepatic bile acid secretion. Its expression levels vary in humans, and it is not clear how these variations affect lipid metabolism. We investigated whether overexpression of Abcb11 in mice increases lipid absorption in the intestine and affects the development of obesity or hypercholesterolemia.

METHODS:

Transgenic mice that overexpress Abcb11 in liver (TTR-Abcb11) and FVB/NJ mice (controls) were fed a high-cholesterol or high-fat diet for 12 weeks. Intestinal lipid absorption was measured by the dual fecal isotope method. Energy expenditure was measured by indirect calorimetry. The bile acid pool was analyzed by high-performance liquid chromatography.

RESULTS:

TTR-Abcb11 mice had a nearly 2-fold increase in intestinal cholesterol absorption compared with controls. TTR-Abcb11 mice fed a high-cholesterol diet had greater increases in plasma and hepatic levels of cholesterol and became more obese than controls; they also had increased intestinal absorption of fatty acids and decreased energy expenditure. In the TTR-Abcb11 mice, the sizes of plasma and total bile acid pools were reduced; the bile acid pool contained more species of hydrophobic bile acids compared with controls.

CONCLUSIONS:

Hepatic overexpression of Abcb11 in mice promotes diet-induced obesity and hypercholesterolemia; increased intestinal cholesterol absorption by hydrophobic bile acids might cause these features. Increased absorption of fatty acids in the intestine and reduced expenditure of energy could increase weight gain in TTR-Abcb11 mice. In humans, variations in expression of ABCB11 might confer genetic susceptibility to diet-induced hyperlipidemia and obesity.

PMID:
21726512
PMCID:
PMC3186850
DOI:
10.1053/j.gastro.2011.06.062
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center