Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance

Autores
Frances, Daniel Eleazar Antonio; Motino, Oscar; Agra, Noelia; Gonzáles Rodriguez, Agueda; Fernández Alvarez, Ana Julia; Cucarella, Carme; Mayoral, Rafael; Castro Sánchez, Luis; García Casarrubios, Ester; Boscá, Lisardo; Carnovale, Cristina Ester; Casado, Marta; Valverde, Ángela M.; Martín Sanz, Paloma
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Accumulation evidence links obesity-induced inflammation as an important contributor to the development of insulin resistance which plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes mellitus and non- alcoholic fatty liver disease. Cyclooxygenase (COX)-1 and -2 catalyze the first step in prostanoid biosynthesis. Since adult hepatocytes fail to induce COX-2 expression regardless of the pro-inflammatory stimuli used, we have evaluated whether this lack of expression under mild pro-inflammatory conditions might constitute a permissive condition for the onset of insulin resistance. Our results show that constitutive expression of human COX-2 (hCOX-2) in hepatocytes protects against adiposity, inflammation, and hence insulin resistance induced by high fat diet as demonstrated by decreased hepatic steatosis, adiposity, plasmatic and hepatic triglycerides and free fatty acids, increased adiponectin/leptin ratio and decreased levels of pro-inflammatory cytokines together with an enhancement of insulin sensitivity and glucose tolerance. Furthermore, hCOX-2 transgenic mice exhibited increased whole body energy expenditure due in part by induction of thermogenesis and fatty acid oxidation. The analysis of hepatic insulin signaling revealed an increase in insulin receptor-mediated Akt phosphorylation in hCOX-2-Tg. In conclusion, our results point to COX-2 as a potential therapeutic target against obesity-associated metabolic dysfunction.
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Motino, Oscar. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: Agra, Noelia. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: Gonzáles Rodriguez, Agueda. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERDEM; España
Fil: Fernández Alvarez, Ana Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Cucarella, Carme. Consejo Superior de Investigaciones Científicas. Instituto de Biomedicina de Valencia. Biomedical Institute of Valencia; España
Fil: Mayoral, Rafael. CIBERehd; España. University Of California At San Diego; Estados Unidos
Fil: Castro Sánchez, Luis. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: García Casarrubios, Ester. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: Boscá, Lisardo. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERehd; España
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Casado, Marta. Consejo Superior de Investigaciones Científicas. Instituto de Biomedicina de Valencia. Biomedical Institute of Valencia; España. CIBERehd; España
Fil: Valverde, Ángela M.. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERDEM; España
Fil: Martín Sanz, Paloma. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERehd; España
Materia
Hepatic Cyclooxygenase-2
Diet-Induced Steatosis
Obesity
Insulin Resistance
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:11336/6095
Acceder
id CONICETDig_20c9ba8c656baf59cdc7f5a56700e38a
oai_identifier_str oai:ri.conicet.gov.ar:11336/6095
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistanceFrances, Daniel Eleazar AntonioMotino, OscarAgra, NoeliaGonzáles Rodriguez, AguedaFernández Alvarez, Ana JuliaCucarella, CarmeMayoral, RafaelCastro Sánchez, LuisGarcía Casarrubios, EsterBoscá, LisardoCarnovale, Cristina EsterCasado, MartaValverde, Ángela M.Martín Sanz, PalomaHepatic Cyclooxygenase-2Diet-Induced SteatosisObesityInsulin Resistancehttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Accumulation evidence links obesity-induced inflammation as an important contributor to the development of insulin resistance which plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes mellitus and non- alcoholic fatty liver disease. Cyclooxygenase (COX)-1 and -2 catalyze the first step in prostanoid biosynthesis. Since adult hepatocytes fail to induce COX-2 expression regardless of the pro-inflammatory stimuli used, we have evaluated whether this lack of expression under mild pro-inflammatory conditions might constitute a permissive condition for the onset of insulin resistance. Our results show that constitutive expression of human COX-2 (hCOX-2) in hepatocytes protects against adiposity, inflammation, and hence insulin resistance induced by high fat diet as demonstrated by decreased hepatic steatosis, adiposity, plasmatic and hepatic triglycerides and free fatty acids, increased adiponectin/leptin ratio and decreased levels of pro-inflammatory cytokines together with an enhancement of insulin sensitivity and glucose tolerance. Furthermore, hCOX-2 transgenic mice exhibited increased whole body energy expenditure due in part by induction of thermogenesis and fatty acid oxidation. The analysis of hepatic insulin signaling revealed an increase in insulin receptor-mediated Akt phosphorylation in hCOX-2-Tg. In conclusion, our results point to COX-2 as a potential therapeutic target against obesity-associated metabolic dysfunction.Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Motino, Oscar. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; EspañaFil: Agra, Noelia. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; EspañaFil: Gonzáles Rodriguez, Agueda. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERDEM; EspañaFil: Fernández Alvarez, Ana Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Cucarella, Carme. Consejo Superior de Investigaciones Científicas. Instituto de Biomedicina de Valencia. Biomedical Institute of Valencia; EspañaFil: Mayoral, Rafael. CIBERehd; España. University Of California At San Diego; Estados UnidosFil: Castro Sánchez, Luis. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; EspañaFil: García Casarrubios, Ester. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; EspañaFil: Boscá, Lisardo. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERehd; EspañaFil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); ArgentinaFil: Casado, Marta. Consejo Superior de Investigaciones Científicas. Instituto de Biomedicina de Valencia. Biomedical Institute of Valencia; España. CIBERehd; EspañaFil: Valverde, Ángela M.. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERDEM; EspañaFil: Martín Sanz, Paloma. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERehd; EspañaAmerican Diabetes Association2015-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/6095Frances, Daniel Eleazar Antonio; Motino, Oscar; Agra, Noelia; Gonzáles Rodriguez, Agueda; Fernández Alvarez, Ana Julia; et al.; Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance; American Diabetes Association; Diabetes; 64; 5; 1-2015; 1522-15310012-1797enginfo:eu-repo/semantics/altIdentifier/url/http://diabetes.diabetesjournals.org/content/64/5/1522.longinfo:eu-repo/semantics/altIdentifier/doi/10.2337/db14-0979info:eu-repo/semantics/altIdentifier/doi/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:02Zoai:ri.conicet.gov.ar:11336/6095instacron: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:34982025-09-29 09:59:03.077CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance
title Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance
spellingShingle Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance
Frances, Daniel Eleazar Antonio
Hepatic Cyclooxygenase-2
Diet-Induced Steatosis
Obesity
Insulin Resistance
title_short Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance
title_full Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance
title_fullStr Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance
title_full_unstemmed Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance
title_sort Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance
dc.creator.none.fl_str_mv Frances, Daniel Eleazar Antonio
Motino, Oscar
Agra, Noelia
Gonzáles Rodriguez, Agueda
Fernández Alvarez, Ana Julia
Cucarella, Carme
Mayoral, Rafael
Castro Sánchez, Luis
García Casarrubios, Ester
Boscá, Lisardo
Carnovale, Cristina Ester
Casado, Marta
Valverde, Ángela M.
Martín Sanz, Paloma
author Frances, Daniel Eleazar Antonio
author_facet Frances, Daniel Eleazar Antonio
Motino, Oscar
Agra, Noelia
Gonzáles Rodriguez, Agueda
Fernández Alvarez, Ana Julia
Cucarella, Carme
Mayoral, Rafael
Castro Sánchez, Luis
García Casarrubios, Ester
Boscá, Lisardo
Carnovale, Cristina Ester
Casado, Marta
Valverde, Ángela M.
Martín Sanz, Paloma
author_role author
author2 Motino, Oscar
Agra, Noelia
Gonzáles Rodriguez, Agueda
Fernández Alvarez, Ana Julia
Cucarella, Carme
Mayoral, Rafael
Castro Sánchez, Luis
García Casarrubios, Ester
Boscá, Lisardo
Carnovale, Cristina Ester
Casado, Marta
Valverde, Ángela M.
Martín Sanz, Paloma
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Hepatic Cyclooxygenase-2
Diet-Induced Steatosis
Obesity
Insulin Resistance
topic Hepatic Cyclooxygenase-2
Diet-Induced Steatosis
Obesity
Insulin Resistance
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Accumulation evidence links obesity-induced inflammation as an important contributor to the development of insulin resistance which plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes mellitus and non- alcoholic fatty liver disease. Cyclooxygenase (COX)-1 and -2 catalyze the first step in prostanoid biosynthesis. Since adult hepatocytes fail to induce COX-2 expression regardless of the pro-inflammatory stimuli used, we have evaluated whether this lack of expression under mild pro-inflammatory conditions might constitute a permissive condition for the onset of insulin resistance. Our results show that constitutive expression of human COX-2 (hCOX-2) in hepatocytes protects against adiposity, inflammation, and hence insulin resistance induced by high fat diet as demonstrated by decreased hepatic steatosis, adiposity, plasmatic and hepatic triglycerides and free fatty acids, increased adiponectin/leptin ratio and decreased levels of pro-inflammatory cytokines together with an enhancement of insulin sensitivity and glucose tolerance. Furthermore, hCOX-2 transgenic mice exhibited increased whole body energy expenditure due in part by induction of thermogenesis and fatty acid oxidation. The analysis of hepatic insulin signaling revealed an increase in insulin receptor-mediated Akt phosphorylation in hCOX-2-Tg. In conclusion, our results point to COX-2 as a potential therapeutic target against obesity-associated metabolic dysfunction.
Fil: Frances, Daniel Eleazar Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Motino, Oscar. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: Agra, Noelia. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: Gonzáles Rodriguez, Agueda. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERDEM; España
Fil: Fernández Alvarez, Ana Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Cucarella, Carme. Consejo Superior de Investigaciones Científicas. Instituto de Biomedicina de Valencia. Biomedical Institute of Valencia; España
Fil: Mayoral, Rafael. CIBERehd; España. University Of California At San Diego; Estados Unidos
Fil: Castro Sánchez, Luis. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: García Casarrubios, Ester. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España
Fil: Boscá, Lisardo. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERehd; España
Fil: Carnovale, Cristina Ester. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
Fil: Casado, Marta. Consejo Superior de Investigaciones Científicas. Instituto de Biomedicina de Valencia. Biomedical Institute of Valencia; España. CIBERehd; España
Fil: Valverde, Ángela M.. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERDEM; España
Fil: Martín Sanz, Paloma. Consejo Superior de Investigaciones Científicas. Instituto de Investigaciones Biomédicas "Alberto Sols"; España. CIBERehd; España
description Accumulation evidence links obesity-induced inflammation as an important contributor to the development of insulin resistance which plays a key role in the pathophysiology of obesity-related diseases such as type 2 diabetes mellitus and non- alcoholic fatty liver disease. Cyclooxygenase (COX)-1 and -2 catalyze the first step in prostanoid biosynthesis. Since adult hepatocytes fail to induce COX-2 expression regardless of the pro-inflammatory stimuli used, we have evaluated whether this lack of expression under mild pro-inflammatory conditions might constitute a permissive condition for the onset of insulin resistance. Our results show that constitutive expression of human COX-2 (hCOX-2) in hepatocytes protects against adiposity, inflammation, and hence insulin resistance induced by high fat diet as demonstrated by decreased hepatic steatosis, adiposity, plasmatic and hepatic triglycerides and free fatty acids, increased adiponectin/leptin ratio and decreased levels of pro-inflammatory cytokines together with an enhancement of insulin sensitivity and glucose tolerance. Furthermore, hCOX-2 transgenic mice exhibited increased whole body energy expenditure due in part by induction of thermogenesis and fatty acid oxidation. The analysis of hepatic insulin signaling revealed an increase in insulin receptor-mediated Akt phosphorylation in hCOX-2-Tg. In conclusion, our results point to COX-2 as a potential therapeutic target against obesity-associated metabolic dysfunction.
publishDate 2015
dc.date.none.fl_str_mv 2015-01
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/11336/6095
Frances, Daniel Eleazar Antonio; Motino, Oscar; Agra, Noelia; Gonzáles Rodriguez, Agueda; Fernández Alvarez, Ana Julia; et al.; Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance; American Diabetes Association; Diabetes; 64; 5; 1-2015; 1522-1531
0012-1797
url http://hdl.handle.net/11336/6095
identifier_str_mv Frances, Daniel Eleazar Antonio; Motino, Oscar; Agra, Noelia; Gonzáles Rodriguez, Agueda; Fernández Alvarez, Ana Julia; et al.; Hepatic cyclooxygenase-2 expression protects against diet-induced steatosis, obesity and insulin resistance; American Diabetes Association; Diabetes; 64; 5; 1-2015; 1522-1531
0012-1797
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://diabetes.diabetesjournals.org/content/64/5/1522.long
info:eu-repo/semantics/altIdentifier/doi/10.2337/db14-0979
info:eu-repo/semantics/altIdentifier/doi/
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
application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Diabetes Association
publisher.none.fl_str_mv American Diabetes Association
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 13.070432

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