title: Hepatic overexpression of abcb11 promotes hypercholesterolemia and obesity in mice.
abstract: OBJECTIVE
  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.
authors: Division of Hepatology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
authors: Anne S
authors: AS
authors: Henkel
authors: Mark H
authors: MH
authors: Kavesh
authors: Michael S
authors: MS
authors: Kriss
authors: Amanda M
authors: AM
authors: Dewey
authors: Mary E
authors: ME
authors: Rinella
authors: Richard M
authors: RM
authors: Green
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002153:Calorimetry, Indirect; D002791:Cholesterol, Dietary / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004734:Energy Metabolism; D005227:Fatty Acids / Q000378:metabolism; D005838:Genotype; D057927:Hydrophobic and Hydrophilic Interactions; D006937:Hypercholesterolemia / Q000235:genetics / Q000378:metabolism*; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D011228:Prealbumin / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation; D015430:Weight Gain
chemical_list: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490549:Abcb11 protein, mouse; D001647:Bile Acids and Salts; D002791:Cholesterol, Dietary; D005227:Fatty Acids; D011228:Prealbumin