The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes

Detalhes bibliográficos
Autor(a) principal: Lemos, Vera
Data de Publicação: 2017
Outros Autores: de Oliveira, Rita M., Naia, Luana, Szegö, Éva, Ramos, Elisabete, Pinho, Sónia, Magro, Fernando, Cavadas, Cláudia, Cristina Rego, A., Costa, Vítor, Outeiro, Tiago F., Gomes, Pedro
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/149358
Resumo: Funding Information: European Regional Development Fund (ERDF), Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000012: HealthyAging2020); COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-007440, SFRH/BPD/109347/ 2015 to R.M.O., SFRH/BD/86655/2012 to L.N. and SFRH/BPD/ 111815/2015 to P.G.); FLAD Life Science 2020 Grant to A.C.R.; European Molecular Biology Organization (EMBO Installation Grant to T.F.O.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) to T.F.O.
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spelling The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytesMolecular BiologyGeneticsGenetics(clinical)SDG 3 - Good Health and Well-beingFunding Information: European Regional Development Fund (ERDF), Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000012: HealthyAging2020); COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-007440, SFRH/BPD/109347/ 2015 to R.M.O., SFRH/BD/86655/2012 to L.N. and SFRH/BPD/ 111815/2015 to P.G.); FLAD Life Science 2020 Grant to A.C.R.; European Molecular Biology Organization (EMBO Installation Grant to T.F.O.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) to T.F.O.Insulin resistance is a major predictor of the development of metabolic disorders. Sirtuins (SIRTs) have emerged as potential targets that can be manipulated to counteract age-related diseases, including type 2 diabetes. SIRT2 has been recently shown to exert important metabolic effects, but whether SIRT2 regulates insulin sensitivity in hepatocytes is currently unknown. The aim of this study is to investigate this possibility and to elucidate underlying molecular mechanisms. Here, we show that SIRT2 is downregulated in insulin-resistant hepatocytes and livers, and this was accompanied by increased generation of reactive oxygen species, activation of stress-sensitive ERK1/2 kinase, and mitochondrial dysfunction. Conversely, SIRT2 overexpression in insulin-resistant hepatocytes improved insulin sensitivity, mitigated reactive oxygen species production and ameliorated mitochondrial dysfunction. Further analysis revealed a reestablishment of mitochondrial morphology, with a higher number of elongated mitochondria rather than fragmented mitochondria instigated by insulin resistance. Mechanistically, SIRT2 was able to increase fusion-related protein Mfn2 and decrease mitochondrial-associated Drp1. SIRT2 also attenuated the downregulation of TFAM, a key mtDNA-associated protein, contributing to the increase in mitochondrial mass. Importantly, we found that SIRT2 expression in PBMCs of human subjects was negatively correlated with obesity and insulin resistance. These results suggest a novel function for hepatic SIRT2 in the regulation of insulin sensitivity and raise the possibility that SIRT2 activators may offer novel opportunities for preventing or treating insulin resistance and type 2 diabetes.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNLemos, Verade Oliveira, Rita M.Naia, LuanaSzegö, ÉvaRamos, ElisabetePinho, SóniaMagro, FernandoCavadas, CláudiaCristina Rego, A.Costa, VítorOuteiro, Tiago F.Gomes, Pedro2023-02-16T22:23:38Z2017-11-012017-11-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttp://hdl.handle.net/10362/149358eng0964-6906PURE: 53478878https://doi.org/10.1093/hmg/ddx298info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-05-22T18:09:18Zoai:run.unl.pt:10362/149358Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-05-22T18:09:18Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes
title The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes
spellingShingle The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes
Lemos, Vera
Molecular Biology
Genetics
Genetics(clinical)
SDG 3 - Good Health and Well-being
title_short The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes
title_full The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes
title_fullStr The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes
title_full_unstemmed The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes
title_sort The NAD+-dependent deacetylase SIRT2 attenuates oxidative stress and mitochondrial dysfunction and improves insulin sensitivity in hepatocytes
author Lemos, Vera
author_facet Lemos, Vera
de Oliveira, Rita M.
Naia, Luana
Szegö, Éva
Ramos, Elisabete
Pinho, Sónia
Magro, Fernando
Cavadas, Cláudia
Cristina Rego, A.
Costa, Vítor
Outeiro, Tiago F.
Gomes, Pedro
author_role author
author2 de Oliveira, Rita M.
Naia, Luana
Szegö, Éva
Ramos, Elisabete
Pinho, Sónia
Magro, Fernando
Cavadas, Cláudia
Cristina Rego, A.
Costa, Vítor
Outeiro, Tiago F.
Gomes, Pedro
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv Lemos, Vera
de Oliveira, Rita M.
Naia, Luana
Szegö, Éva
Ramos, Elisabete
Pinho, Sónia
Magro, Fernando
Cavadas, Cláudia
Cristina Rego, A.
Costa, Vítor
Outeiro, Tiago F.
Gomes, Pedro
dc.subject.por.fl_str_mv Molecular Biology
Genetics
Genetics(clinical)
SDG 3 - Good Health and Well-being
topic Molecular Biology
Genetics
Genetics(clinical)
SDG 3 - Good Health and Well-being
description Funding Information: European Regional Development Fund (ERDF), Centro 2020 Regional Operational Programme (CENTRO-01-0145-FEDER-000012: HealthyAging2020); COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation and Portuguese national funds via FCT – Fundação para a Ciência e a Tecnologia (POCI-01-0145-FEDER-007440, SFRH/BPD/109347/ 2015 to R.M.O., SFRH/BD/86655/2012 to L.N. and SFRH/BPD/ 111815/2015 to P.G.); FLAD Life Science 2020 Grant to A.C.R.; European Molecular Biology Organization (EMBO Installation Grant to T.F.O.); DFG Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB) to T.F.O.
publishDate 2017
dc.date.none.fl_str_mv 2017-11-01
2017-11-01T00:00:00Z
2023-02-16T22:23:38Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/149358
url http://hdl.handle.net/10362/149358
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0964-6906
PURE: 53478878
https://doi.org/10.1093/hmg/ddx298
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13
application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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