Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity

Background and Purpose Obesity is a risk factor for the development of chronic kidney disease independent of diabetes, hypertension and other co-morbidities. Obesity-associated nephropathy is linked to dysregulation of the cell energy sensor AMP-activated protein kinase (AMPK). We aimed here to asse...

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Autores: Rodríguez Prados, Claudia, Sánchez Pina, Ana Alejandra, Sáenz Medina, Javier, Muñoz Picos, Mercedes, Hernández Rodríguez, Medardo Vicente, López, Miguel, Rivera De Los Arcos, Luis, Contreras Jiménez, Cristina, Prieto Ocejo, Dolores
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/6814
Acceso en línea:https://hdl.handle.net/20.500.14352/6814
Access Level:acceso abierto
Palabra clave:612
616.61
616-056.25
AMPK
Endothelial dysfunction
Inflammation
Kidney
Oobesity
Oxidative stress
Fisiología
Nefrología y urología
Fisiología animal (Farmacia)
2411 Fisiología Humana
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oai_identifier_str oai:docta.ucm.es:20.500.14352/6814
network_acronym_str ES
network_name_str España
repository_id_str
spelling Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesityRodríguez Prados, ClaudiaSánchez Pina, Ana AlejandraSáenz Medina, JavierMuñoz Picos, MercedesHernández Rodríguez, Medardo VicenteLópez, MiguelRivera De Los Arcos, LuisContreras Jiménez, CristinaPrieto Ocejo, Dolores612616.61616-056.25AMPKEndothelial dysfunctionInflammationKidneyOobesityOxidative stressFisiologíaNefrología y urologíaFisiología animal (Farmacia)2411 Fisiología HumanaBackground and Purpose Obesity is a risk factor for the development of chronic kidney disease independent of diabetes, hypertension and other co-morbidities. Obesity-associated nephropathy is linked to dysregulation of the cell energy sensor AMP-activated protein kinase (AMPK). We aimed here to assess whether impairment of AMPK activity may cause renal arterial dysfunction in obesity and to evaluate the therapeutic potential of activating renal AMPK. Experimental Approach Effects of the AMPK activator A769662 were assessed on intrarenal arteries isolated from ob/ob mice and obese Zucker rats and then mounted in microvascular myographs. Superoxide and hydrogen peroxide production were measured by chemiluminescence and fluorescence, respectively, and protein expression was analysed by western blotting. Key Results Endothelium-dependent vasodilation and PI3K/Akt/eNOS pathway were impaired in preglomerular arteries from genetically obese rats and mice, along with impaired arterial AMPK activity and blunted relaxations induced by the AMPK activator A769662. Acute ex vivo exposure to A769662 restored endothelial function and enhanced activity of PI3K/Akt/eNOS pathway in obese rats, whereas in vivo treatment with A769662 improved metabolic state and ameliorated endothelial dysfunction, reduced inflammatory markers and vascular oxidative stress in renal arteries and restored redox balance in renal cortex of obese mice. Conclusion and Implications These results demonstrate that AMPK dysregulation underlies obesity-associated kidney vascular dysfunction and activation of AMPK improves metabolic state, protects renal endothelial function and exerts potent vascular antioxidant and anti-inflammatory effects. The beneficial effects of vascular AMPK activation might represent a promising therapeutic approach to the treatment of obesity-related kidney injury.WileyUniversidad Complutense de Madrid20212021-06-3020212021-06-30journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/6814reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución-NoComercial-SinDerivadas 3.0 Españahttps://creativecommons.org/licenses/by-nc-nd/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/68142026-06-02T12:44:21Z
dc.title.none.fl_str_mv Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity
title Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity
spellingShingle Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity
Rodríguez Prados, Claudia
612
616.61
616-056.25
AMPK
Endothelial dysfunction
Inflammation
Kidney
Oobesity
Oxidative stress
Fisiología
Nefrología y urología
Fisiología animal (Farmacia)
2411 Fisiología Humana
title_short Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity
title_full Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity
title_fullStr Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity
title_full_unstemmed Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity
title_sort Activation of AMP kinase ameliorates kidney vascular dysfunction, oxidative stress and inflammation in rodent models of obesity
dc.creator.none.fl_str_mv Rodríguez Prados, Claudia
Sánchez Pina, Ana Alejandra
Sáenz Medina, Javier
Muñoz Picos, Mercedes
Hernández Rodríguez, Medardo Vicente
López, Miguel
Rivera De Los Arcos, Luis
Contreras Jiménez, Cristina
Prieto Ocejo, Dolores
author Rodríguez Prados, Claudia
author_facet Rodríguez Prados, Claudia
Sánchez Pina, Ana Alejandra
Sáenz Medina, Javier
Muñoz Picos, Mercedes
Hernández Rodríguez, Medardo Vicente
López, Miguel
Rivera De Los Arcos, Luis
Contreras Jiménez, Cristina
Prieto Ocejo, Dolores
author_role author
author2 Sánchez Pina, Ana Alejandra
Sáenz Medina, Javier
Muñoz Picos, Mercedes
Hernández Rodríguez, Medardo Vicente
López, Miguel
Rivera De Los Arcos, Luis
Contreras Jiménez, Cristina
Prieto Ocejo, Dolores
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv 612
616.61
616-056.25
AMPK
Endothelial dysfunction
Inflammation
Kidney
Oobesity
Oxidative stress
Fisiología
Nefrología y urología
Fisiología animal (Farmacia)
2411 Fisiología Humana
topic 612
616.61
616-056.25
AMPK
Endothelial dysfunction
Inflammation
Kidney
Oobesity
Oxidative stress
Fisiología
Nefrología y urología
Fisiología animal (Farmacia)
2411 Fisiología Humana
description Background and Purpose Obesity is a risk factor for the development of chronic kidney disease independent of diabetes, hypertension and other co-morbidities. Obesity-associated nephropathy is linked to dysregulation of the cell energy sensor AMP-activated protein kinase (AMPK). We aimed here to assess whether impairment of AMPK activity may cause renal arterial dysfunction in obesity and to evaluate the therapeutic potential of activating renal AMPK. Experimental Approach Effects of the AMPK activator A769662 were assessed on intrarenal arteries isolated from ob/ob mice and obese Zucker rats and then mounted in microvascular myographs. Superoxide and hydrogen peroxide production were measured by chemiluminescence and fluorescence, respectively, and protein expression was analysed by western blotting. Key Results Endothelium-dependent vasodilation and PI3K/Akt/eNOS pathway were impaired in preglomerular arteries from genetically obese rats and mice, along with impaired arterial AMPK activity and blunted relaxations induced by the AMPK activator A769662. Acute ex vivo exposure to A769662 restored endothelial function and enhanced activity of PI3K/Akt/eNOS pathway in obese rats, whereas in vivo treatment with A769662 improved metabolic state and ameliorated endothelial dysfunction, reduced inflammatory markers and vascular oxidative stress in renal arteries and restored redox balance in renal cortex of obese mice. Conclusion and Implications These results demonstrate that AMPK dysregulation underlies obesity-associated kidney vascular dysfunction and activation of AMPK improves metabolic state, protects renal endothelial function and exerts potent vascular antioxidant and anti-inflammatory effects. The beneficial effects of vascular AMPK activation might represent a promising therapeutic approach to the treatment of obesity-related kidney injury.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021-06-30
2021
2021-06-30
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/6814
url https://hdl.handle.net/20.500.14352/6814
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-SinDerivadas 3.0 España
https://creativecommons.org/licenses/by-nc-nd/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución-NoComercial-SinDerivadas 3.0 España
https://creativecommons.org/licenses/by-nc-nd/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Wiley
publisher.none.fl_str_mv Wiley
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869411432728100864
score 15.300719

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