Effects of bile acid sequestration on hepatic steatosis in obese mice

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 cholestyrami...

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Main Authors: Nancy Solís, Margarita Pizarro, Pablo Quintero, Juan Pablo Arab, Arnoldo Riquelme, Oslando Padilla, Gonzalo Carrasco, Carlos J. Pirola, Silvia Sookoian, Marco Arrese
Format: Article
Language:English
Published: Elsevier 2014-01-01
Series:Annals of Hepatology
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1665268119309111
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author Nancy Solís
Margarita Pizarro
Pablo Quintero
Juan Pablo Arab
Arnoldo Riquelme
Oslando Padilla
Gonzalo Carrasco
Carlos J. Pirola
Silvia Sookoian
Marco Arrese
author_facet Nancy Solís
Margarita Pizarro
Pablo Quintero
Juan Pablo Arab
Arnoldo Riquelme
Oslando Padilla
Gonzalo Carrasco
Carlos J. Pirola
Silvia Sookoian
Marco Arrese
author_sort Nancy Solís
collection DOAJ
description 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-Le-pob/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.
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spelling doaj.art-2e355d80233f448dba3e6f1bd7dd108a2022-12-21T21:25:13ZengElsevierAnnals of Hepatology1665-26812014-01-01131105112Effects of bile acid sequestration on hepatic steatosis in obese miceNancy Solís0Margarita Pizarro1Pablo Quintero2Juan Pablo Arab3Arnoldo Riquelme4Oslando Padilla5Gonzalo Carrasco6Carlos J. Pirola7Silvia Sookoian8Marco Arrese9Departamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, ChileDepartamento de Salud Pública, Pontificia Universidad Católica de Chile, Santiago, Chile.Hospital Parroquial de San Bernardo, San Bernardo, ChileInstitute of Medical Research (IDIM), University of Buenos Aires, National Council of Scientific and Technological Research (CONICET), Autonomous City of Buenos Aires 1427, ArgentinaInstitute of Medical Research (IDIM), University of Buenos Aires, National Council of Scientific and Technological Research (CONICET), Autonomous City of Buenos Aires 1427, ArgentinaDepartamento de Gastroenterología, Escuela de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile; Correspondence and reprint request: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-Le-pob/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.http://www.sciencedirect.com/science/article/pii/S1665268119309111NAFLDObese miceBile acidsSteatosisFatty liverCholestyramine
spellingShingle Nancy Solís
Margarita Pizarro
Pablo Quintero
Juan Pablo Arab
Arnoldo Riquelme
Oslando Padilla
Gonzalo Carrasco
Carlos J. Pirola
Silvia Sookoian
Marco Arrese
Effects of bile acid sequestration on hepatic steatosis in obese mice
Annals of Hepatology
NAFLD
Obese mice
Bile acids
Steatosis
Fatty liver
Cholestyramine
title Effects of bile acid sequestration on hepatic steatosis in obese mice
title_full Effects of bile acid sequestration on hepatic steatosis in obese mice
title_fullStr Effects of bile acid sequestration on hepatic steatosis in obese mice
title_full_unstemmed Effects of bile acid sequestration on hepatic steatosis in obese mice
title_short Effects of bile acid sequestration on hepatic steatosis in obese mice
title_sort effects of bile acid sequestration on hepatic steatosis in obese mice
topic NAFLD
Obese mice
Bile acids
Steatosis
Fatty liver
Cholestyramine
url http://www.sciencedirect.com/science/article/pii/S1665268119309111
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