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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/6095
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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 Técnicas2025-09-03T09:55:47Zoai: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:34982025-09-03 09:55:47.956CONICET 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 |
_version_ |
1842269366939287552 |
score |
13.13397 |