Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement
Autor(a) principal: | |
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Data de Publicação: | 2018 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/s12944-018-0714-8 http://hdl.handle.net/11449/164801 |
Resumo: | Background: Obesity is strongly associated to insulin resistance, inflammation, and elevated plasma free fatty acids, but the mechanisms behind this association are not fully comprehended. Evidences suggest that endoplasmic reticulum (ER) stress may play a role in this complex pathophysiology. The aim of the present study was to investigate the involvement of inflammation and ER stress in the modulation of glucose transporter GLUT4, encoded by Slc2a4 gene, in L6 skeletal muscle cells. Methods: L6 cells were acutely (2 h) and chronically (6 and 12 h) exposed to palmitate, and the expression of several proteins involved in insulin resistance, ER stress and inflammation were analyzed. Results: Chronic and acute palmitate exposure significantly reduced GLUT4 protein (similar to 39%, P < 0.01) and its mRNA (18%, P < 0.01) expression. Only acute palmitate treatment increased GRP78 (28%, P < 0.05), PERK (98%, P < 0.01), eIF-2A (35%, P < 0.01), IRE1a (60%, P < 0.05) and TRAF2 (23%, P < 0.05) protein content, and PERK phosphorylation (106%, P < 0.001), but did not elicit eIF-2A, IKK phosphorylation or increased XBP1 nuclear content. Additionally, acute and chronic palmitate increased NFKB p65 nuclear content (similar to 30%, P < 0.05) and NFKB binding activity to Slc2a4 gene promoter (similar to 45%, P < 0.05). Conclusion: Different pathways are activated in acute and chronic palmitate induced-repression of Slc2a4/GLUT4 expression. This regulation involves activation of initial component of ER stress, such as the formation of a IRE1a-TRAF2-IKK complex, and converges to NFKB-induced repression of Slc2a4/GLUT4. These results link ER stress, inflammation and insulin resistance in L6 cells. |
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Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvementPalmitateGLUT4ER stressNFKBL6 cellsInsulin resistanceBackground: Obesity is strongly associated to insulin resistance, inflammation, and elevated plasma free fatty acids, but the mechanisms behind this association are not fully comprehended. Evidences suggest that endoplasmic reticulum (ER) stress may play a role in this complex pathophysiology. The aim of the present study was to investigate the involvement of inflammation and ER stress in the modulation of glucose transporter GLUT4, encoded by Slc2a4 gene, in L6 skeletal muscle cells. Methods: L6 cells were acutely (2 h) and chronically (6 and 12 h) exposed to palmitate, and the expression of several proteins involved in insulin resistance, ER stress and inflammation were analyzed. Results: Chronic and acute palmitate exposure significantly reduced GLUT4 protein (similar to 39%, P < 0.01) and its mRNA (18%, P < 0.01) expression. Only acute palmitate treatment increased GRP78 (28%, P < 0.05), PERK (98%, P < 0.01), eIF-2A (35%, P < 0.01), IRE1a (60%, P < 0.05) and TRAF2 (23%, P < 0.05) protein content, and PERK phosphorylation (106%, P < 0.001), but did not elicit eIF-2A, IKK phosphorylation or increased XBP1 nuclear content. Additionally, acute and chronic palmitate increased NFKB p65 nuclear content (similar to 30%, P < 0.05) and NFKB binding activity to Slc2a4 gene promoter (similar to 45%, P < 0.05). Conclusion: Different pathways are activated in acute and chronic palmitate induced-repression of Slc2a4/GLUT4 expression. This regulation involves activation of initial component of ER stress, such as the formation of a IRE1a-TRAF2-IKK complex, and converges to NFKB-induced repression of Slc2a4/GLUT4. These results link ER stress, inflammation and insulin resistance in L6 cells.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Av Prof Lineu Prestes 1524, BR-05508900 Sao Paulo, BrazilUniv Estadual Paulista, Sch Sci & Technol, Dept Phys Therapy, Sao Paulo, BrazilUniv Estadual Campinas, Dept Pharmacol, Fac Med Sci, Campinas, SP, BrazilUniv Sao Paulo, Hosp Clin HCFMUSP, Lab Lipides LIM 10, Fac Med, Sao Paulo, SP, BrazilUniv Estadual Paulista, Sch Sci & Technol, Dept Phys Therapy, Sao Paulo, BrazilFAPESP: 2010/09984-5FAPESP: 2013/18841-1FAPESP: 2016/15603-1Biomed Central LtdUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Universidade Estadual de Campinas (UNICAMP)Ebersbach-Silva, PatriciaPoletto, Ana ClaudiaDavid-Silva, AlineSeraphim, Patricia Monteiro [UNESP]Anhe, Gabriel ForatoPassarelli, MarisaFuruya, Daniela TomieMachado, Ubiratan Fabres2018-11-26T20:08:58Z2018-11-26T20:08:58Z2018-04-02info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article8application/pdfhttp://dx.doi.org/10.1186/s12944-018-0714-8Lipids In Health And Disease. London: Biomed Central Ltd, v. 17, 8 p., 2018.1476-511Xhttp://hdl.handle.net/11449/16480110.1186/s12944-018-0714-8WOS:000428898600003WOS000428898600003.pdf04110085990708710000-0003-2145-6640Web of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengLipids In Health And Diseaseinfo:eu-repo/semantics/openAccess2023-12-21T06:25:16Zoai:repositorio.unesp.br:11449/164801Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:57:11.199949Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement |
title |
Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement |
spellingShingle |
Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement Ebersbach-Silva, Patricia Palmitate GLUT4 ER stress NFKB L6 cells Insulin resistance |
title_short |
Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement |
title_full |
Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement |
title_fullStr |
Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement |
title_full_unstemmed |
Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement |
title_sort |
Palmitate-induced Slc2a4/GLUT4 downregulation in L6 muscle cells: evidence of inflammatory and endoplasmic reticulum stress involvement |
author |
Ebersbach-Silva, Patricia |
author_facet |
Ebersbach-Silva, Patricia Poletto, Ana Claudia David-Silva, Aline Seraphim, Patricia Monteiro [UNESP] Anhe, Gabriel Forato Passarelli, Marisa Furuya, Daniela Tomie Machado, Ubiratan Fabres |
author_role |
author |
author2 |
Poletto, Ana Claudia David-Silva, Aline Seraphim, Patricia Monteiro [UNESP] Anhe, Gabriel Forato Passarelli, Marisa Furuya, Daniela Tomie Machado, Ubiratan Fabres |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) Universidade Estadual de Campinas (UNICAMP) |
dc.contributor.author.fl_str_mv |
Ebersbach-Silva, Patricia Poletto, Ana Claudia David-Silva, Aline Seraphim, Patricia Monteiro [UNESP] Anhe, Gabriel Forato Passarelli, Marisa Furuya, Daniela Tomie Machado, Ubiratan Fabres |
dc.subject.por.fl_str_mv |
Palmitate GLUT4 ER stress NFKB L6 cells Insulin resistance |
topic |
Palmitate GLUT4 ER stress NFKB L6 cells Insulin resistance |
description |
Background: Obesity is strongly associated to insulin resistance, inflammation, and elevated plasma free fatty acids, but the mechanisms behind this association are not fully comprehended. Evidences suggest that endoplasmic reticulum (ER) stress may play a role in this complex pathophysiology. The aim of the present study was to investigate the involvement of inflammation and ER stress in the modulation of glucose transporter GLUT4, encoded by Slc2a4 gene, in L6 skeletal muscle cells. Methods: L6 cells were acutely (2 h) and chronically (6 and 12 h) exposed to palmitate, and the expression of several proteins involved in insulin resistance, ER stress and inflammation were analyzed. Results: Chronic and acute palmitate exposure significantly reduced GLUT4 protein (similar to 39%, P < 0.01) and its mRNA (18%, P < 0.01) expression. Only acute palmitate treatment increased GRP78 (28%, P < 0.05), PERK (98%, P < 0.01), eIF-2A (35%, P < 0.01), IRE1a (60%, P < 0.05) and TRAF2 (23%, P < 0.05) protein content, and PERK phosphorylation (106%, P < 0.001), but did not elicit eIF-2A, IKK phosphorylation or increased XBP1 nuclear content. Additionally, acute and chronic palmitate increased NFKB p65 nuclear content (similar to 30%, P < 0.05) and NFKB binding activity to Slc2a4 gene promoter (similar to 45%, P < 0.05). Conclusion: Different pathways are activated in acute and chronic palmitate induced-repression of Slc2a4/GLUT4 expression. This regulation involves activation of initial component of ER stress, such as the formation of a IRE1a-TRAF2-IKK complex, and converges to NFKB-induced repression of Slc2a4/GLUT4. These results link ER stress, inflammation and insulin resistance in L6 cells. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-11-26T20:08:58Z 2018-11-26T20:08:58Z 2018-04-02 |
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://dx.doi.org/10.1186/s12944-018-0714-8 Lipids In Health And Disease. London: Biomed Central Ltd, v. 17, 8 p., 2018. 1476-511X http://hdl.handle.net/11449/164801 10.1186/s12944-018-0714-8 WOS:000428898600003 WOS000428898600003.pdf 0411008599070871 0000-0003-2145-6640 |
url |
http://dx.doi.org/10.1186/s12944-018-0714-8 http://hdl.handle.net/11449/164801 |
identifier_str_mv |
Lipids In Health And Disease. London: Biomed Central Ltd, v. 17, 8 p., 2018. 1476-511X 10.1186/s12944-018-0714-8 WOS:000428898600003 WOS000428898600003.pdf 0411008599070871 0000-0003-2145-6640 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Lipids In Health And Disease |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
8 application/pdf |
dc.publisher.none.fl_str_mv |
Biomed Central Ltd |
publisher.none.fl_str_mv |
Biomed Central Ltd |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
_version_ |
1808129266517278720 |