title: Bile acid supplementation improves established liver steatosis in obese mice independently of glucagon-like peptide-1 secretion.
abstract: Bile acids or its derivatives may influence non-alcoholic fatty liver disease development through multiple mechanisms. Intestinal L-cells secrete glucagon-like peptide-1 (GLP-1) and can be activated by bile acids (BA) influencing insulin resistance and hepatic steatosis development and progression. The aim of the present study was to assess the effects of cholic acid (CA) or ursodeoxycholic acid (UDCA) administration on portal and systemic levels of GLP-1 in genetically obese mice with established hepatic steatosis. Eight-week-old ob/ob mice were fed CA or UDCA during 4 weeks. Systemic and portal GLP-1 levels were measured as well as glucose tolerance test, serum and biliary parameters, hepatic triglyceride content, liver histology, and hepatic gene expression of relevant genes related to bile secretion. Eight-week-old ob/ob mice exhibited marked obesity, hyperinsulinemia, and fasting hyperglycemia. Administration of both CA and UDCA was associated to decreased hepatic triglyceride content and complete reversion of histological steatosis. BA-fed animals did not exhibit significant differences in glucose tolerance. In addition, neither CA nor UDCA administration significantly influenced portal or systemic GLP-1 levels. CA and UDCA strongly ameliorated established fatty liver in ob/ob mice independently of the GLP-1 incretin pathway. Thus, the anti-steatotic action of these bile acids is likely related to direct hepatic effects.
authors.affiliation: Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Marcoleta 367, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Quintero
authors.forename: Margarita
authors.initials: M
authors.lastname: Pizarro
authors.forename: Nancy
authors.initials: N
authors.lastname: Solís
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Arab
authors.forename: Oslando
authors.initials: O
authors.lastname: Padilla
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Riquelme
authors.forename: Marco
authors.initials: M
authors.lastname: Arrese
mesh_terms: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D001647:Bile Acids and Salts / Q000008:administration & dosage*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics; D019826:Cholic Acid / Q000008:administration & dosage; D015870:Gene Expression / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000097:blood*; D005951:Glucose Tolerance Test; D054795:Incretins / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D027981:Symporters / Q000235:genetics; D014280:Triglycerides / Q000378:metabolism; D014580:Ursodeoxycholic Acid / Q000008:administration & dosage
chemical_list: D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; C490548:Abcb11 protein, rat; D001647:Bile Acids and Salts; D054795:Incretins; D029363:Organic Anion Transporters, Sodium-Dependent; D018160:Receptors, Cytoplasmic and Nuclear; D027981:Symporters; D014280:Triglycerides; C099713:nuclear receptor subfamily 0, group B, member 2; C071908:sodium-bile acid cotransporter; D014580:Ursodeoxycholic Acid; D052216:Glucagon-Like Peptide 1; C532838:CYP7A1 protein, rat; D002790:Cholesterol 7-alpha-Hydroxylase; D019826:Cholic Acid