Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle

The peroxisome proliferator-activated receptor (PPAR)delta has been implicated in the regulation of lipid metabolism in skeletal muscle. Furthermore, activation of PPARdelta has been proposed to improve insulin sensitivity and reduce glucose levels in animal models of type 2 diabetes. We recently de...

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Autores: Krämer, David Kitz, Al-Khalili, Lubna, Guigas, Bruno, Leng, Ying, García-Roves, Pablo M. (Pablo Miguel), Krook, Anna
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2007
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/177394
Acceso en línea:https://hdl.handle.net/2445/177394
Access Level:acceso abierto
Palabra clave:Expressió gènica
Metabolisme
Glucosa
Lípids
Gene expression
Metabolism
Glucose
Lipids
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spelling Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscleKrämer, David KitzAl-Khalili, LubnaGuigas, BrunoLeng, YingGarcía-Roves, Pablo M. (Pablo Miguel)Krook, AnnaExpressió gènicaMetabolismeGlucosaLípidsGene expressionMetabolismGlucoseLipidsThe peroxisome proliferator-activated receptor (PPAR)delta has been implicated in the regulation of lipid metabolism in skeletal muscle. Furthermore, activation of PPARdelta has been proposed to improve insulin sensitivity and reduce glucose levels in animal models of type 2 diabetes. We recently demonstrated that the PPARdelta agonist GW501516 activates AMP-activated protein kinase (AMPK) and stimulates glucose uptake in skeletal muscle. However, the underlying mechanism remains to be clearly identified. In this study, we first confirmed that incubation of primary cultured human muscle cells with GW501516 induced AMPK phosphorylation and increased fatty acid transport and oxidation and glucose uptake. Using small interfering RNA, we have demonstrated that PPARdelta expression is required for the effect of GW501516 on the intracellular accumulation of fatty acids. Furthermore, we have shown that the subsequent increase in fatty acid oxidation induced by GW501516 is dependent on both PPARdelta and AMPK. Concomitant with these metabolic changes, we provide evidence that GW501516 increases the expression of key genes involved in lipid metabolism (FABP3, CPT1, and PDK4) by a PPARdelta-dependent mechanism. Finally, we have also demonstrated that the GW501516-mediated increase in glucose uptake requires AMPK but not PPARdelta. In conclusion, the PPARdelta agonist GW501516 promotes changes in lipid/glucose metabolism and gene expression in human skeletal muscle cells by PPARdelta- and AMPK-dependent and -independent mechanisms.American Society for Biochemistry and Molecular Biology2007info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/177394Articles publicats en revistes (Ciències Fisiològiques)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésReproducció del document publicat a: https://doi.org/10.1074/jbc.M702329200Journal of Biological Chemistry, 2007, vol. 282, num. 27, p. 19313-19320https://doi.org/10.1074/jbc.M702329200(c) American Society for Biochemistry and Molecular Biology, 2007info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1773942026-05-27T06:46:51Z
dc.title.none.fl_str_mv Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle
title Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle
spellingShingle Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle
Krämer, David Kitz
Expressió gènica
Metabolisme
Glucosa
Lípids
Gene expression
Metabolism
Glucose
Lipids
title_short Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle
title_full Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle
title_fullStr Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle
title_full_unstemmed Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle
title_sort Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle
dc.creator.none.fl_str_mv Krämer, David Kitz
Al-Khalili, Lubna
Guigas, Bruno
Leng, Ying
García-Roves, Pablo M. (Pablo Miguel)
Krook, Anna
author Krämer, David Kitz
author_facet Krämer, David Kitz
Al-Khalili, Lubna
Guigas, Bruno
Leng, Ying
García-Roves, Pablo M. (Pablo Miguel)
Krook, Anna
author_role author
author2 Al-Khalili, Lubna
Guigas, Bruno
Leng, Ying
García-Roves, Pablo M. (Pablo Miguel)
Krook, Anna
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Expressió gènica
Metabolisme
Glucosa
Lípids
Gene expression
Metabolism
Glucose
Lipids
topic Expressió gènica
Metabolisme
Glucosa
Lípids
Gene expression
Metabolism
Glucose
Lipids
description The peroxisome proliferator-activated receptor (PPAR)delta has been implicated in the regulation of lipid metabolism in skeletal muscle. Furthermore, activation of PPARdelta has been proposed to improve insulin sensitivity and reduce glucose levels in animal models of type 2 diabetes. We recently demonstrated that the PPARdelta agonist GW501516 activates AMP-activated protein kinase (AMPK) and stimulates glucose uptake in skeletal muscle. However, the underlying mechanism remains to be clearly identified. In this study, we first confirmed that incubation of primary cultured human muscle cells with GW501516 induced AMPK phosphorylation and increased fatty acid transport and oxidation and glucose uptake. Using small interfering RNA, we have demonstrated that PPARdelta expression is required for the effect of GW501516 on the intracellular accumulation of fatty acids. Furthermore, we have shown that the subsequent increase in fatty acid oxidation induced by GW501516 is dependent on both PPARdelta and AMPK. Concomitant with these metabolic changes, we provide evidence that GW501516 increases the expression of key genes involved in lipid metabolism (FABP3, CPT1, and PDK4) by a PPARdelta-dependent mechanism. Finally, we have also demonstrated that the GW501516-mediated increase in glucose uptake requires AMPK but not PPARdelta. In conclusion, the PPARdelta agonist GW501516 promotes changes in lipid/glucose metabolism and gene expression in human skeletal muscle cells by PPARdelta- and AMPK-dependent and -independent mechanisms.
publishDate 2007
dc.date.none.fl_str_mv 2007
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/177394
url https://hdl.handle.net/2445/177394
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1074/jbc.M702329200
Journal of Biological Chemistry, 2007, vol. 282, num. 27, p. 19313-19320
https://doi.org/10.1074/jbc.M702329200
dc.rights.none.fl_str_mv (c) American Society for Biochemistry and Molecular Biology, 2007
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Society for Biochemistry and Molecular Biology, 2007
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
publisher.none.fl_str_mv American Society for Biochemistry and Molecular Biology
dc.source.none.fl_str_mv Articles publicats en revistes (Ciències Fisiològiques)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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