N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats

Autores
Villagarcía, Hernán Gonzalo; Castro, María Cecilia; González Arbeláez, Luisa Fernanda; Schinella, Guillermo Raúl; Massa, Maria Laura; Spinedi, Eduardo Julio; Francini, Flavio
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
AimHypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammation and, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctions and, liver OS and inflammation in both monosodium l-glutamate (MSG)-neonatally damaged and control litter-mate (C) adult male rats, either chronically treated with N-Acetyl-l-Cysteine since weaned (C-NAC and MSG-NAC) or not.MethodologyWe evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate and alanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity ?LISI-) were calculated and liver steps of the insulin-signaling pathway were investigated. Additionally, we monitored liver OS (protein carbonyl groups, GSH and iNOS level) and inflammation-related markers (COX-2 and TNFα protein content; gene expression level of Il1b, Tnfα and Pai-1); and carbohydrate and lipid metabolic functions (glucokinase/fructokinase activities and, mRNA levels of Srebp1c, Fas and Gpat).Key FindingsChronic NAC treatment in MSG rats efficiently decreased the high circulating levels of triglycerides, UA, transaminases and TBARS, as well as peripheral (high insulinemia and HOMA indexes) and liver (LISI and the P-AKT:AKT and P-eNOS:eNOS protein ratio values) insulin-resistance. Moreover, NAC therapy in MSG rats prevented liver dysmetabolism by decreasing local levels of OS and inflammation markers. Finally, NAC-treated MSG rats retained normal liver glucokinase and fructokinase activities, and Srebp1c, Fas and Gpat (lipogenic genes) expression levels.SignificanceOur study strongly supports that chronic oral antioxidant therapy (NAC administration) prevented the development of pre-diabetes, dyslipidemia, and inflamed-dysmetabolic liver in hypothalamic obese rats by efficiently decreasing high endogenous OS.
Fil: Villagarcía, Hernán Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
Fil: González Arbeláez, Luisa Fernanda. Universidad Nacional de La Plata; Argentina
Fil: Schinella, Guillermo Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
Fil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
Fil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
Materia
MSG-damaged rat
Liver dysfunction
Oxidative stress
Metabolic syndrome
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/89432
Acceder
id CONICETDig_0ddb79bcb5e5bd8d606487830a97131f
oai_identifier_str oai:ri.conicet.gov.ar:11336/89432
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese ratsVillagarcía, Hernán GonzaloCastro, María CeciliaGonzález Arbeláez, Luisa FernandaSchinella, Guillermo RaúlMassa, Maria LauraSpinedi, Eduardo JulioFrancini, FlavioMSG-damaged ratLiver dysfunctionOxidative stressMetabolic syndromehttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3AimHypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammation and, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctions and, liver OS and inflammation in both monosodium l-glutamate (MSG)-neonatally damaged and control litter-mate (C) adult male rats, either chronically treated with N-Acetyl-l-Cysteine since weaned (C-NAC and MSG-NAC) or not.MethodologyWe evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate and alanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity ?LISI-) were calculated and liver steps of the insulin-signaling pathway were investigated. Additionally, we monitored liver OS (protein carbonyl groups, GSH and iNOS level) and inflammation-related markers (COX-2 and TNFα protein content; gene expression level of Il1b, Tnfα and Pai-1); and carbohydrate and lipid metabolic functions (glucokinase/fructokinase activities and, mRNA levels of Srebp1c, Fas and Gpat).Key FindingsChronic NAC treatment in MSG rats efficiently decreased the high circulating levels of triglycerides, UA, transaminases and TBARS, as well as peripheral (high insulinemia and HOMA indexes) and liver (LISI and the P-AKT:AKT and P-eNOS:eNOS protein ratio values) insulin-resistance. Moreover, NAC therapy in MSG rats prevented liver dysmetabolism by decreasing local levels of OS and inflammation markers. Finally, NAC-treated MSG rats retained normal liver glucokinase and fructokinase activities, and Srebp1c, Fas and Gpat (lipogenic genes) expression levels.SignificanceOur study strongly supports that chronic oral antioxidant therapy (NAC administration) prevented the development of pre-diabetes, dyslipidemia, and inflamed-dysmetabolic liver in hypothalamic obese rats by efficiently decreasing high endogenous OS.Fil: Villagarcía, Hernán Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; ArgentinaFil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; ArgentinaFil: González Arbeláez, Luisa Fernanda. Universidad Nacional de La Plata; ArgentinaFil: Schinella, Guillermo Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; ArgentinaFil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; ArgentinaFil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; ArgentinaPergamon-Elsevier Science Ltd2018-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/89432Villagarcía, Hernán Gonzalo; Castro, María Cecilia; González Arbeláez, Luisa Fernanda; Schinella, Guillermo Raúl; Massa, Maria Laura; et al.; N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats; Pergamon-Elsevier Science Ltd; Life Sciences; 199; 4-2018; 88-950024-3205CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S0024320518301061info:eu-repo/semantics/altIdentifier/doi/10.1016/j.lfs.2018.03.008info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:22:06Zoai:ri.conicet.gov.ar:11336/89432instacron: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:34982025-10-15 14:22:06.753CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats
title N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats
spellingShingle N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats
Villagarcía, Hernán Gonzalo
MSG-damaged rat
Liver dysfunction
Oxidative stress
Metabolic syndrome
title_short N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats
title_full N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats
title_fullStr N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats
title_full_unstemmed N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats
title_sort N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats
dc.creator.none.fl_str_mv Villagarcía, Hernán Gonzalo
Castro, María Cecilia
González Arbeláez, Luisa Fernanda
Schinella, Guillermo Raúl
Massa, Maria Laura
Spinedi, Eduardo Julio
Francini, Flavio
author Villagarcía, Hernán Gonzalo
author_facet Villagarcía, Hernán Gonzalo
Castro, María Cecilia
González Arbeláez, Luisa Fernanda
Schinella, Guillermo Raúl
Massa, Maria Laura
Spinedi, Eduardo Julio
Francini, Flavio
author_role author
author2 Castro, María Cecilia
González Arbeláez, Luisa Fernanda
Schinella, Guillermo Raúl
Massa, Maria Laura
Spinedi, Eduardo Julio
Francini, Flavio
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv MSG-damaged rat
Liver dysfunction
Oxidative stress
Metabolic syndrome
topic MSG-damaged rat
Liver dysfunction
Oxidative stress
Metabolic syndrome
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv AimHypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammation and, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctions and, liver OS and inflammation in both monosodium l-glutamate (MSG)-neonatally damaged and control litter-mate (C) adult male rats, either chronically treated with N-Acetyl-l-Cysteine since weaned (C-NAC and MSG-NAC) or not.MethodologyWe evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate and alanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity ?LISI-) were calculated and liver steps of the insulin-signaling pathway were investigated. Additionally, we monitored liver OS (protein carbonyl groups, GSH and iNOS level) and inflammation-related markers (COX-2 and TNFα protein content; gene expression level of Il1b, Tnfα and Pai-1); and carbohydrate and lipid metabolic functions (glucokinase/fructokinase activities and, mRNA levels of Srebp1c, Fas and Gpat).Key FindingsChronic NAC treatment in MSG rats efficiently decreased the high circulating levels of triglycerides, UA, transaminases and TBARS, as well as peripheral (high insulinemia and HOMA indexes) and liver (LISI and the P-AKT:AKT and P-eNOS:eNOS protein ratio values) insulin-resistance. Moreover, NAC therapy in MSG rats prevented liver dysmetabolism by decreasing local levels of OS and inflammation markers. Finally, NAC-treated MSG rats retained normal liver glucokinase and fructokinase activities, and Srebp1c, Fas and Gpat (lipogenic genes) expression levels.SignificanceOur study strongly supports that chronic oral antioxidant therapy (NAC administration) prevented the development of pre-diabetes, dyslipidemia, and inflamed-dysmetabolic liver in hypothalamic obese rats by efficiently decreasing high endogenous OS.
Fil: Villagarcía, Hernán Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
Fil: Castro, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
Fil: González Arbeláez, Luisa Fernanda. Universidad Nacional de La Plata; Argentina
Fil: Schinella, Guillermo Raúl. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina
Fil: Massa, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
Fil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
Fil: Francini, Flavio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnol.conicet - la Plata. Centro de Endocrinología Exp.y Aplicada (i). Grupo Vinculado Cenexa-fcex-unlp; Argentina
description AimHypothalamic obese rats are characterized by pre-diabetes, dyslipidemia, hyperadiposity, inflammation and, liver dysmetabolism with oxidative stress (OS), among others. We studied endocrine-metabolic dysfunctions and, liver OS and inflammation in both monosodium l-glutamate (MSG)-neonatally damaged and control litter-mate (C) adult male rats, either chronically treated with N-Acetyl-l-Cysteine since weaned (C-NAC and MSG-NAC) or not.MethodologyWe evaluated circulating TBARS, glucose, insulin, triglycerides, uric acid (UA) and, aspartate and alanine amino-transferase; insulin sensitivity markers (HOMA indexes, Liver Index of Insulin Sensitivity ?LISI-) were calculated and liver steps of the insulin-signaling pathway were investigated. Additionally, we monitored liver OS (protein carbonyl groups, GSH and iNOS level) and inflammation-related markers (COX-2 and TNFα protein content; gene expression level of Il1b, Tnfα and Pai-1); and carbohydrate and lipid metabolic functions (glucokinase/fructokinase activities and, mRNA levels of Srebp1c, Fas and Gpat).Key FindingsChronic NAC treatment in MSG rats efficiently decreased the high circulating levels of triglycerides, UA, transaminases and TBARS, as well as peripheral (high insulinemia and HOMA indexes) and liver (LISI and the P-AKT:AKT and P-eNOS:eNOS protein ratio values) insulin-resistance. Moreover, NAC therapy in MSG rats prevented liver dysmetabolism by decreasing local levels of OS and inflammation markers. Finally, NAC-treated MSG rats retained normal liver glucokinase and fructokinase activities, and Srebp1c, Fas and Gpat (lipogenic genes) expression levels.SignificanceOur study strongly supports that chronic oral antioxidant therapy (NAC administration) prevented the development of pre-diabetes, dyslipidemia, and inflamed-dysmetabolic liver in hypothalamic obese rats by efficiently decreasing high endogenous OS.
publishDate 2018
dc.date.none.fl_str_mv 2018-04
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/11336/89432
Villagarcía, Hernán Gonzalo; Castro, María Cecilia; González Arbeláez, Luisa Fernanda; Schinella, Guillermo Raúl; Massa, Maria Laura; et al.; N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats; Pergamon-Elsevier Science Ltd; Life Sciences; 199; 4-2018; 88-95
0024-3205
CONICET Digital
CONICET
url http://hdl.handle.net/11336/89432
identifier_str_mv Villagarcía, Hernán Gonzalo; Castro, María Cecilia; González Arbeláez, Luisa Fernanda; Schinella, Guillermo Raúl; Massa, Maria Laura; et al.; N -Acetyl- l -Cysteine treatment efficiently prevented pre-diabetes and inflamed-dysmetabolic liver development in hypothalamic obese rats; Pergamon-Elsevier Science Ltd; Life Sciences; 199; 4-2018; 88-95
0024-3205
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S0024320518301061
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.lfs.2018.03.008
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
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dc.publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
publisher.none.fl_str_mv Pergamon-Elsevier Science Ltd
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
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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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