title: CLA-enriched diet containing t10,c12-CLA alters bile acid homeostasis and increases the risk of cholelithiasis in mice.
abstract: Mice fed a mixture of CLA containing t10,c12-CLA lose fat mass and develop hyperinsulinemia and hepatic steatosis due to an accumulation of TG and cholesterol. Because cholesterol is the precursor in bile acid (BA) synthesis, we investigated whether t10,c12-CLA alters BA metabolism. In Expt. 1, female C57Bl/6J mice were fed a standard diet for 28 d supplemented with a CLA mixture (1 g/100 g) or not (controls). In Expt. 2, the feeding period was reduced to 4, 6, and 10 d. In Expt. 3, mice were fed a diet supplemented with linoleic acid, c9,t11-CLA, or t10,c12-CLA (0.4 g/100 g) for 28 d. In Expt. 1, the BA pool size was greater in CLA-fed mice than in controls and the entero-hepatic circulation of BA was altered due to greater BA synthesis and ileal reclamation. This resulted from higher hepatic cholesterol 7α-hydroxylase (CYP7A1) and ileal apical sodium BA transporter expressions in CLA-fed mice. Furthermore, hepatic Na(+)/taurocholate co-transporting polypeptide (NTCP) (-52%) and bile salt export pump (BSEP) (-77%) protein levels were lower in CLA-fed mice than in controls, leading to a greater accumulation of BA in the plasma (+500%); also, the cholesterol saturation index and the concentration of hydrophobic BA in the bile were greater in CLA-fed mice, changes associated with the presence of cholesterol crystals. Expt. 2 suggests that CLA-mediated changes were caused by hyperinsulinemia, which occurred after 6 d of the CLA diet before NTCP and BSEP mRNA downregulation (10 d). Expt. 3 demonstrated that only t10,c12-CLA altered NTCP and BSEP mRNA levels. In conclusion, t10,c12-CLA alters BA homeostasis and increases the risk of cholelithiasis in mice.
authors.affiliation: Physiologie de la Nutrition, UMR INSERM U 866/ Université de Bourgogne, AgroSup Dijon, 21000 Dijon, France.
authors.forename: Amaia Zabala
authors.initials: AZ
authors.lastname: Letona
authors.forename: Isabelle
authors.initials: I
authors.lastname: Niot
authors.forename: Fabienne
authors.initials: F
authors.lastname: Laugerette
authors.forename: Anne
authors.initials: A
authors.lastname: Athias
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Monnot
authors.forename: Maria P
authors.initials: MP
authors.lastname: Portillo
authors.forename: Philippe
authors.initials: P
authors.lastname: Besnard
authors.forename: Hélène
authors.initials: H
authors.lastname: Poirier
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D015153:Blotting, Western; D002769:Cholelithiasis / Q000209:etiology*; D002784:Cholesterol / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage*; D005260:Female; D006706:Homeostasis; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012307:Risk Factors; D017962:alpha-Linolenic Acid / Q000008:administration & dosage*
chemical_list: D001647:Bile Acids and Salts; D004041:Dietary Fats; D017962:alpha-Linolenic Acid; D002784:Cholesterol