Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet

Autores
Castro, María Cecilia; Massa, Maria Laura; Schinella, Guillermo Raúl; Gagliardino, Juan Jose; Francini, Flavio
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: To evaluate whether co-administration of R/S-α-lipoic acid can prevent the development of oxidative stress and metabolic changes induced by a fructose-rich diet (F). Methods: We assessed glycemia in the fasting state and during an oral glucose tolerance test, triglyceridemia and insulinemia in rats fed with standard diet (control) and fructose without or with R/S-α-lipoic acid. Insulin resistance and hepatic insulin sensitivity were also calculated. In liver, we measured reduced glutathione, protein carbonyl groups, antioxidant capacity by ABTS assay, antioxidant enzymes (catalase and superoxide dismutase 1 and 2), uncoupling protein 2, PPARδ and PPARγ protein expressions, SREBP-1c, fatty acid synthase and glycerol-3-phosphate acyltransferase-1 gene expression, and glucokinase activity. Results: R/S-α-lipoic acid co-administration to F-fed rats a) prevented hyperinsulinemia, hypertriglyceridemia and insulin resistance, b) improved hepatic insulin sensitivity and glucose tolerance, c) decreased liver oxidative stress and increased antioxidant capacity and antioxidant enzymes expression, d) decreased uncoupling protein 2 and PPARδ protein expression and increased PPARγ levels, e) restored the basal gene expression of PPARδ, SREBP-1c and the lipogenic genes fatty acid synthase and glycerol-3-phosphate acyltransferase, and f) decreased the fructose-mediated enhancement of glucokinase activity. Conclusions: Our results suggest that fructose-induced oxidative stress is an early phenomenon associated with compensatory hepatic metabolic mechanisms, and that treatment with an antioxidant prevented the development of such changes. General significance: This knowledge would help to better understand the mechanisms involved in liver adaptation to fructose-induced oxidative stress and to develop effective strategies to prevent and treat, at early stages, obesity and type 2 diabetes mellitus.
Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina
Fil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina
Fil: Schinella, Guillermo Raúl. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina
Fil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina
Materia
Fructose
Liver Uncoupling Protein 2
Ppar Regulation
R/S-Alpha-Lipoic Acid
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/5290
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/5290
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich dietCastro, María CeciliaMassa, Maria LauraSchinella, Guillermo RaúlGagliardino, Juan JoseFrancini, FlavioFructoseLiver Uncoupling Protein 2Ppar RegulationR/S-Alpha-Lipoic Acidhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: To evaluate whether co-administration of R/S-α-lipoic acid can prevent the development of oxidative stress and metabolic changes induced by a fructose-rich diet (F). Methods: We assessed glycemia in the fasting state and during an oral glucose tolerance test, triglyceridemia and insulinemia in rats fed with standard diet (control) and fructose without or with R/S-α-lipoic acid. Insulin resistance and hepatic insulin sensitivity were also calculated. In liver, we measured reduced glutathione, protein carbonyl groups, antioxidant capacity by ABTS assay, antioxidant enzymes (catalase and superoxide dismutase 1 and 2), uncoupling protein 2, PPARδ and PPARγ protein expressions, SREBP-1c, fatty acid synthase and glycerol-3-phosphate acyltransferase-1 gene expression, and glucokinase activity. Results: R/S-α-lipoic acid co-administration to F-fed rats a) prevented hyperinsulinemia, hypertriglyceridemia and insulin resistance, b) improved hepatic insulin sensitivity and glucose tolerance, c) decreased liver oxidative stress and increased antioxidant capacity and antioxidant enzymes expression, d) decreased uncoupling protein 2 and PPARδ protein expression and increased PPARγ levels, e) restored the basal gene expression of PPARδ, SREBP-1c and the lipogenic genes fatty acid synthase and glycerol-3-phosphate acyltransferase, and f) decreased the fructose-mediated enhancement of glucokinase activity. Conclusions: Our results suggest that fructose-induced oxidative stress is an early phenomenon associated with compensatory hepatic metabolic mechanisms, and that treatment with an antioxidant prevented the development of such changes. General significance: This knowledge would help to better understand the mechanisms involved in liver adaptation to fructose-induced oxidative stress and to develop effective strategies to prevent and treat, at early stages, obesity and type 2 diabetes mellitus.Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Schinella, Guillermo Raúl. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaFil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); ArgentinaElsevier2013-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/5290Castro, María Cecilia; Massa, Maria Laura; Schinella, Guillermo Raúl; Gagliardino, Juan Jose; Francini, Flavio; Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet; Elsevier; Biochimica et Biophysica Acta- General Subjects; 1830; 1; 1-2013; 2226-22320304-4165enginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0304416512002905info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbagen.2012.10.010info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-17T11:15:51Zoai:ri.conicet.gov.ar:11336/5290instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-17 11:15:52.099CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet
title Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet
spellingShingle Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet
Castro, María Cecilia
Fructose
Liver Uncoupling Protein 2
Ppar Regulation
R/S-Alpha-Lipoic Acid
title_short Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet
title_full Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet
title_fullStr Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet
title_full_unstemmed Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet
title_sort Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet
dc.creator.none.fl_str_mv Castro, María Cecilia
Massa, Maria Laura
Schinella, Guillermo Raúl
Gagliardino, Juan Jose
Francini, Flavio
author Castro, María Cecilia
author_facet Castro, María Cecilia
Massa, Maria Laura
Schinella, Guillermo Raúl
Gagliardino, Juan Jose
Francini, Flavio
author_role author
author2 Massa, Maria Laura
Schinella, Guillermo Raúl
Gagliardino, Juan Jose
Francini, Flavio
author2_role author
author
author
author
dc.subject.none.fl_str_mv Fructose
Liver Uncoupling Protein 2
Ppar Regulation
R/S-Alpha-Lipoic Acid
topic Fructose
Liver Uncoupling Protein 2
Ppar Regulation
R/S-Alpha-Lipoic Acid
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: To evaluate whether co-administration of R/S-α-lipoic acid can prevent the development of oxidative stress and metabolic changes induced by a fructose-rich diet (F). Methods: We assessed glycemia in the fasting state and during an oral glucose tolerance test, triglyceridemia and insulinemia in rats fed with standard diet (control) and fructose without or with R/S-α-lipoic acid. Insulin resistance and hepatic insulin sensitivity were also calculated. In liver, we measured reduced glutathione, protein carbonyl groups, antioxidant capacity by ABTS assay, antioxidant enzymes (catalase and superoxide dismutase 1 and 2), uncoupling protein 2, PPARδ and PPARγ protein expressions, SREBP-1c, fatty acid synthase and glycerol-3-phosphate acyltransferase-1 gene expression, and glucokinase activity. Results: R/S-α-lipoic acid co-administration to F-fed rats a) prevented hyperinsulinemia, hypertriglyceridemia and insulin resistance, b) improved hepatic insulin sensitivity and glucose tolerance, c) decreased liver oxidative stress and increased antioxidant capacity and antioxidant enzymes expression, d) decreased uncoupling protein 2 and PPARδ protein expression and increased PPARγ levels, e) restored the basal gene expression of PPARδ, SREBP-1c and the lipogenic genes fatty acid synthase and glycerol-3-phosphate acyltransferase, and f) decreased the fructose-mediated enhancement of glucokinase activity. Conclusions: Our results suggest that fructose-induced oxidative stress is an early phenomenon associated with compensatory hepatic metabolic mechanisms, and that treatment with an antioxidant prevented the development of such changes. General significance: This knowledge would help to better understand the mechanisms involved in liver adaptation to fructose-induced oxidative stress and to develop effective strategies to prevent and treat, at early stages, obesity and type 2 diabetes mellitus.
Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina
Fil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina
Fil: Schinella, Guillermo Raúl. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; Argentina
Fil: Gagliardino, Juan Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina
Fil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico La Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina
description Background: To evaluate whether co-administration of R/S-α-lipoic acid can prevent the development of oxidative stress and metabolic changes induced by a fructose-rich diet (F). Methods: We assessed glycemia in the fasting state and during an oral glucose tolerance test, triglyceridemia and insulinemia in rats fed with standard diet (control) and fructose without or with R/S-α-lipoic acid. Insulin resistance and hepatic insulin sensitivity were also calculated. In liver, we measured reduced glutathione, protein carbonyl groups, antioxidant capacity by ABTS assay, antioxidant enzymes (catalase and superoxide dismutase 1 and 2), uncoupling protein 2, PPARδ and PPARγ protein expressions, SREBP-1c, fatty acid synthase and glycerol-3-phosphate acyltransferase-1 gene expression, and glucokinase activity. Results: R/S-α-lipoic acid co-administration to F-fed rats a) prevented hyperinsulinemia, hypertriglyceridemia and insulin resistance, b) improved hepatic insulin sensitivity and glucose tolerance, c) decreased liver oxidative stress and increased antioxidant capacity and antioxidant enzymes expression, d) decreased uncoupling protein 2 and PPARδ protein expression and increased PPARγ levels, e) restored the basal gene expression of PPARδ, SREBP-1c and the lipogenic genes fatty acid synthase and glycerol-3-phosphate acyltransferase, and f) decreased the fructose-mediated enhancement of glucokinase activity. Conclusions: Our results suggest that fructose-induced oxidative stress is an early phenomenon associated with compensatory hepatic metabolic mechanisms, and that treatment with an antioxidant prevented the development of such changes. General significance: This knowledge would help to better understand the mechanisms involved in liver adaptation to fructose-induced oxidative stress and to develop effective strategies to prevent and treat, at early stages, obesity and type 2 diabetes mellitus.
publishDate 2013
dc.date.none.fl_str_mv 2013-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/5290
Castro, María Cecilia; Massa, Maria Laura; Schinella, Guillermo Raúl; Gagliardino, Juan Jose; Francini, Flavio; Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet; Elsevier; Biochimica et Biophysica Acta- General Subjects; 1830; 1; 1-2013; 2226-2232
0304-4165
url http://hdl.handle.net/11336/5290
identifier_str_mv Castro, María Cecilia; Massa, Maria Laura; Schinella, Guillermo Raúl; Gagliardino, Juan Jose; Francini, Flavio; Lipoic acid prevents liver metabolic changes induced by administration of a fructose-rich diet; Elsevier; Biochimica et Biophysica Acta- General Subjects; 1830; 1; 1-2013; 2226-2232
0304-4165
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S0304416512002905
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bbagen.2012.10.010
info:eu-repo/semantics/altIdentifier/doi/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.001348

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