title: Effects of bile acid sequestration on hepatic steatosis in obese mice.
abstract: BACKGROUND. Bile acid sequestration (BAS) with resins has shown antidiabetic effects in both humans and animals. Since hepatic steatosis is commonly associated with type 2 diabetes mellitus and the effects of BAS on steatosis have not been explored in detail, we evaluated the effects of cholestyramine (CTM) administration on fatty liver development in the leptin-deficient obese mice. AIM. To study the effects of BAS on fatty liver development in obese (ob/ob) mice. MATERIAL AND METHODS. 4 week-old ob/ob mice (B6.V-Lepob/J, n = 4-6 per group) were fed with or without CTM (control group) during 8 weeks. Serum and biliary parameters, glucose tolerance test (GTT), hepatic triglyceride content, liver histology and hepatic gene expression of relevant genes related to bile secretion, lipid and glucose metabolism were assessed. RESULTS. Control 12-week-old mice exhibited marked obesity and hepatic steatosis. CTM administration expectedly determined a marked de-repression of 7-α-hydroxylase and decreased biliary bile acid secretion as well as improved GTT. CTM feeding showed no effects on hepatic triglyceride content or in the degree of steatosis on liver histology. CTM was associated with increased levels of serum alanine-aminotransferase. CONCLUSION. Although CTM administration positively affects glucose tolerance it does not prevent hepatic steatosis development in obese mice. Moreover, CTM feeding was associated to liver enzyme elevation in this model of NAFLD. Thus, the effects BAS on NAFLD need to be specifically addressed since this therapy might not be beneficial for this condition.
authors.affiliation: Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Nancy
authors.initials: N
authors.lastname: Solís
authors.affiliation: Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Margarita
authors.initials: M
authors.lastname: Pizarro
authors.affiliation: Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Pablo
authors.initials: P
authors.lastname: Quintero
authors.affiliation: Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Juan Pablo
authors.initials: JP
authors.lastname: Arab
authors.affiliation: Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Arnoldo
authors.initials: A
authors.lastname: Riquelme
authors.affiliation: Departamento de Salud Pública, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Oslando
authors.initials: O
authors.lastname: Padilla
authors.affiliation: Hospital Parroquial de San Bernardo, San Bernardo, Chile.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Carrasco
authors.affiliation: Institute of Medical Research (IDIM), University of Buenos Aires, National Council of Scientific and Technological Research (CONICET), Autonomous City of Buenos Aires 1427, Argentina.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Pirola
authors.affiliation: Institute of Medical Research (IDIM), University of Buenos Aires, National Council of Scientific and Technological Research (CONICET), Autonomous City of Buenos Aires 1427, Argentina.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sookoian
authors.affiliation: Departamento de Gastroenterología, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Marco
authors.initials: M
authors.lastname: Arrese
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001647:Bile Acids and Salts / Q000378:metabolism*; D002792:Cholestyramine Resin / Q000494:pharmacology* / Q000627:therapeutic use; D005234:Fatty Liver / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D020738:Leptin / Q000172:deficiency; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D014280:Triglycerides
chemical_list: D000924:Anticholesteremic Agents; D001647:Bile Acids and Salts; D020738:Leptin; D014280:Triglycerides; D002792:Cholestyramine Resin; D005947:Glucose