Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal
FATP1 mediates skeletal muscle cell fatty acid import, yet its intracellular localization and metabolic control role are not completely defined. Here, we examine FATP1 localization and metabolic effects of its overexpression in mouse skeletal muscle. The FATP1 protein was detected in mitochondrial a...
| Autores: | , , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2014 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/59231 |
| Acceso en línea: | https://hdl.handle.net/2445/59231 |
| Access Level: | acceso abierto |
| Palabra clave: | Aparell locomotor Metabolisme energètic Glicogen Àcids grassos Diabetis Proteïnes de membrana Mitocondris Musculoskeletal system Energy metabolism Glycogen Fatty acids Diabetes Membrane proteins Mitochondria |
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Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposalGuitart de la Rosa, MariaOsorio Conles, ÓscarPentinat Pelegrin, ThaisCebrià, JudithGarcía Villoria, JuditSala Cano, DavidSebastián Muñoz, DavidZorzano Olarte, AntonioRibes Rubió, Maria AntòniaJiménez Chillarón, José CarlosGarcía Martínez, CeliaGómez Foix, Anna MariaAparell locomotorMetabolisme energèticGlicogenÀcids grassosDiabetisProteïnes de membranaMitocondrisMusculoskeletal systemEnergy metabolismGlycogenFatty acidsDiabetesMembrane proteinsMitochondriaFATP1 mediates skeletal muscle cell fatty acid import, yet its intracellular localization and metabolic control role are not completely defined. Here, we examine FATP1 localization and metabolic effects of its overexpression in mouse skeletal muscle. The FATP1 protein was detected in mitochondrial and plasma membrane fractions, obtained by differential centrifugation, of mouse gastrocnemius muscle. FATP1 was most abundant in purified mitochondria, and in the outer membrane and soluble intermembrane, but not in the inner membrane plus matrix, enriched subfractions of purified mitochondria. Immunogold electron microscopy localized FATP1-GFP in mitochondria of transfected C2C12 myotubes. FATP1 was overexpressed in gastrocnemius mouse muscle, by adenovirus-mediated delivery of the gene into hindlimb muscles of newborn mice, fed after weaning a chow or high-fat diet. Compared to GFP delivery, FATP1 did not alter body weight, serum fed glucose, insulin and triglyceride levels, and whole-body glucose tolerance, in either diet. However, fatty acid levels were lower and beta-hydroxybutyrate levels were higher in FATP1-than GFP-mice, irrespective of diet. Moreover, intramuscular triglyceride content was lower in FATP1-versus GFP-mice regardless of diet, and beta-hydroxybutyrate content was unchanged in high-fat-fed mice. Electroporation-mediated FATP1 overexpression enhanced palmitate oxidation to CO2, but not to acid-soluble intermediate metabolites, while CO2 production from beta-hydroxybutyrate was inhibited and that from glucose unchanged, in isolated mouse gastrocnemius strips. In summary, FATP1 was localized in mitochondria, in the outer membrane and intermembrane parts, of mouse skeletal muscle, what may be crucial for its metabolic effects. Overexpressed FATP1 enhanced disposal of both systemic fatty acids and intramuscular triglycerides. Consistently, it did not contribute to the high-fat diet-induced metabolic dysregulation. However, FATP1 lead to hyperketonemia, likely secondary to the sparing of ketone body oxidation by the enhanced oxidation of fatty acids.Public Library of Science (PLoS)2014201420142014info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion15 p.application/pdfhttps://hdl.handle.net/2445/59231Articles publicats en revistes (Bioquímica i Biomedicina Molecular)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0098109PLoS One, 2014, vol. 9, num. 5, p. e98109http://dx.doi.org/10.1371/journal.pone.0098109cc-by (c) Guitart de la Rosa, Maria et al., 2014http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/592312026-05-29T05:05:01Z |
| dc.title.none.fl_str_mv |
Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal |
| title |
Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal |
| spellingShingle |
Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal Guitart de la Rosa, Maria Aparell locomotor Metabolisme energètic Glicogen Àcids grassos Diabetis Proteïnes de membrana Mitocondris Musculoskeletal system Energy metabolism Glycogen Fatty acids Diabetes Membrane proteins Mitochondria |
| title_short |
Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal |
| title_full |
Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal |
| title_fullStr |
Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal |
| title_full_unstemmed |
Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal |
| title_sort |
Fatty acid transport protein 1 (FATP1) delivered into skeletal muscle localizes in mitochondria and regulates lipid and ketone body disposal |
| dc.creator.none.fl_str_mv |
Guitart de la Rosa, Maria Osorio Conles, Óscar Pentinat Pelegrin, Thais Cebrià, Judith García Villoria, Judit Sala Cano, David Sebastián Muñoz, David Zorzano Olarte, Antonio Ribes Rubió, Maria Antònia Jiménez Chillarón, José Carlos García Martínez, Celia Gómez Foix, Anna Maria |
| author |
Guitart de la Rosa, Maria |
| author_facet |
Guitart de la Rosa, Maria Osorio Conles, Óscar Pentinat Pelegrin, Thais Cebrià, Judith García Villoria, Judit Sala Cano, David Sebastián Muñoz, David Zorzano Olarte, Antonio Ribes Rubió, Maria Antònia Jiménez Chillarón, José Carlos García Martínez, Celia Gómez Foix, Anna Maria |
| author_role |
author |
| author2 |
Osorio Conles, Óscar Pentinat Pelegrin, Thais Cebrià, Judith García Villoria, Judit Sala Cano, David Sebastián Muñoz, David Zorzano Olarte, Antonio Ribes Rubió, Maria Antònia Jiménez Chillarón, José Carlos García Martínez, Celia Gómez Foix, Anna Maria |
| author2_role |
author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
Aparell locomotor Metabolisme energètic Glicogen Àcids grassos Diabetis Proteïnes de membrana Mitocondris Musculoskeletal system Energy metabolism Glycogen Fatty acids Diabetes Membrane proteins Mitochondria |
| topic |
Aparell locomotor Metabolisme energètic Glicogen Àcids grassos Diabetis Proteïnes de membrana Mitocondris Musculoskeletal system Energy metabolism Glycogen Fatty acids Diabetes Membrane proteins Mitochondria |
| description |
FATP1 mediates skeletal muscle cell fatty acid import, yet its intracellular localization and metabolic control role are not completely defined. Here, we examine FATP1 localization and metabolic effects of its overexpression in mouse skeletal muscle. The FATP1 protein was detected in mitochondrial and plasma membrane fractions, obtained by differential centrifugation, of mouse gastrocnemius muscle. FATP1 was most abundant in purified mitochondria, and in the outer membrane and soluble intermembrane, but not in the inner membrane plus matrix, enriched subfractions of purified mitochondria. Immunogold electron microscopy localized FATP1-GFP in mitochondria of transfected C2C12 myotubes. FATP1 was overexpressed in gastrocnemius mouse muscle, by adenovirus-mediated delivery of the gene into hindlimb muscles of newborn mice, fed after weaning a chow or high-fat diet. Compared to GFP delivery, FATP1 did not alter body weight, serum fed glucose, insulin and triglyceride levels, and whole-body glucose tolerance, in either diet. However, fatty acid levels were lower and beta-hydroxybutyrate levels were higher in FATP1-than GFP-mice, irrespective of diet. Moreover, intramuscular triglyceride content was lower in FATP1-versus GFP-mice regardless of diet, and beta-hydroxybutyrate content was unchanged in high-fat-fed mice. Electroporation-mediated FATP1 overexpression enhanced palmitate oxidation to CO2, but not to acid-soluble intermediate metabolites, while CO2 production from beta-hydroxybutyrate was inhibited and that from glucose unchanged, in isolated mouse gastrocnemius strips. In summary, FATP1 was localized in mitochondria, in the outer membrane and intermembrane parts, of mouse skeletal muscle, what may be crucial for its metabolic effects. Overexpressed FATP1 enhanced disposal of both systemic fatty acids and intramuscular triglycerides. Consistently, it did not contribute to the high-fat diet-induced metabolic dysregulation. However, FATP1 lead to hyperketonemia, likely secondary to the sparing of ketone body oxidation by the enhanced oxidation of fatty acids. |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014 2014 2014 2014 |
| 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/2445/59231 |
| url |
https://hdl.handle.net/2445/59231 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
Reproducció del document publicat a: http://dx.doi.org/10.1371/journal.pone.0098109 PLoS One, 2014, vol. 9, num. 5, p. e98109 http://dx.doi.org/10.1371/journal.pone.0098109 |
| dc.rights.none.fl_str_mv |
cc-by (c) Guitart de la Rosa, Maria et al., 2014 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by (c) Guitart de la Rosa, Maria et al., 2014 http://creativecommons.org/licenses/by/3.0/es |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
15 p. application/pdf |
| dc.publisher.none.fl_str_mv |
Public Library of Science (PLoS) |
| publisher.none.fl_str_mv |
Public Library of Science (PLoS) |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Bioquímica i Biomedicina Molecular) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
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Recercat. Dipósit de la Recerca de Catalunya |
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Recercat. Dipósit de la Recerca de Catalunya |
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