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dc.contributor.author
Baumann, Anja
dc.contributor.author
Burger, Katharina
dc.contributor.author
Brandt, Annette
dc.contributor.author
Staltner, Raphaela
dc.contributor.author
Jung, Finn
dc.contributor.author
Rajcic, Dragana
dc.contributor.author
Lorenzo Pisarello, Maria Jose
dc.contributor.author
Bergheim, Ina
dc.date.available
2022-06-22T14:52:09Z
dc.date.issued
2022-05-29
dc.identifier.citation
Baumann, Anja; Burger, Katharina; Brandt, Annette; Staltner, Raphaela; Jung, Finn; et al.; GW9662, a peroxisome proliferator-activated receptor gamma antagonist, attenuates the development of non-alcoholic fatty liver disease; Elsevier; Metabolism-clinical And Experimental; 133; 29-5-2022; 1-11
dc.identifier.issn
0026-0495
dc.identifier.uri
http://hdl.handle.net/11336/160203
dc.description.abstract
Background and aims: Insulin resistance is among the key risk factors for the development of non-alcoholic fatty liver disease (NAFLD). Recently, it has been reported that GW9662, shown to be a potent peroxisome proliferator-activated receptor gamma (PPARγ) antagonist, may improve insulin sensitivity in settings of type 2 diabetes. Here, we determined the effects of GW9662 on the development of NAFLD and molecular mechanisms involved. Methods: Female C57BL/6J mice were pair-fed either a liquid control diet (C) or a fat-, fructose- and cholesterol-rich diet (FFC) for 8 weeks while either being treated with GW9662 (1 mg/kg body weight; C+GW9662 and FFC+GW9662) or vehicle (C and FFC) i.p. three times weekly. Indices of liver damage and inflammation, parameters of glucose metabolism and portal endotoxin levels were determined. Lipopolysaccharide (LPS)-challenged J774A.1 cells were treated with 10 μM GW9662. Results: Despite similar caloric intake the development of NAFLD and insulin resistance were significantly attenuated in FFC+GW9662-treated mice when compared to FFC-fed animals. Bacterial endotoxin levels in portal plasma were almost similarly increased in both FFC-fed groups while expressions of toll-like receptor 4 (Tlr4), myeloid differentiation primary response 88 (Myd88) and interleukin 1 beta (Il1b) as well as nitrite (NO2−) concentration in liver were significantly higher in FFC-fed mice than in FFC+GW9662-treated animals. In J774A.1 cells, treatment with GW9662 significantly attenuated LPS-induced expression of Il1b, interleukin 6 (Il6) and inducible nitric oxide synthase (iNos) as well as NO2− formation. Conclusion: In summary, our data suggest that the PPARγ antagonist GW9662 attenuates the development of a diet-induced NAFLD and that this is associated with a protection against the activation of the TLR4 signaling cascade.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
ENDOTOXIN
dc.subject
GLUCOSE TOLERANCE
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INFLAMMATION
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NON-ALCOHOLIC STEATOHEPATITIS
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PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA
dc.subject.classification
Otras Ciencias de la Salud
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Ciencias de la Salud
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CIENCIAS MÉDICAS Y DE LA SALUD
dc.title
GW9662, a peroxisome proliferator-activated receptor gamma antagonist, attenuates the development of non-alcoholic fatty liver disease
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-06-16T19:28:34Z
dc.identifier.eissn
1532-8600
dc.journal.volume
133
dc.journal.pagination
1-11
dc.journal.pais
Estados Unidos
dc.journal.ciudad
Philadelphia
dc.conicet.avisoEditorial
Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
dc.description.fil
Fil: Baumann, Anja. Universidad de Viena; Austria
dc.description.fil
Fil: Burger, Katharina. Universidad de Viena; Austria
dc.description.fil
Fil: Brandt, Annette. Universidad de Viena; Austria
dc.description.fil
Fil: Staltner, Raphaela. Universidad de Viena; Austria
dc.description.fil
Fil: Jung, Finn. Universidad de Viena; Austria
dc.description.fil
Fil: Rajcic, Dragana. Universidad de Viena; Austria
dc.description.fil
Fil: Lorenzo Pisarello, Maria Jose. Universidad de Viena; Austria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Centro de Referencia para Lactobacilos; Argentina
dc.description.fil
Fil: Bergheim, Ina. Universidad de Viena; Austria
dc.journal.title
Metabolism-clinical And Experimental
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.metabol.2022.155233
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0026049522001111
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