Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation

Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is...

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Authors: Malandrino, Maria Ida, Fucho Salvador, Raquel, Weber Blattes, Minéia, Calderón Domínguez, María, Mir Bonnín, Joan Francesc, Valcarcel-Jimenez, Lorea, Escoté, Xavier, Gómez-Serrano, María, Peral, Belén, Salvadó Serra, Laia, Casals i Farré, Núria, Villarroya i Gombau, Francesc, Vázquez Carrera, Manuel, Vendrell, Joan, Serra i Cucurull, Dolors, Herrero Rodríguez, Laura
Format: article
Status:Versión aceptada para publicación
Publication Date:2015
Country:España
Institution:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repository:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/65775
Online Access:https://hdl.handle.net/2445/65775
Access Level:Open access
Keyword:Obesitat
Diabetis no-insulinodependent
Àcids grassos
Inflamació
Macròfags
Obesity
Non-insulin-dependent diabetes
Fatty acids
Inflammation
Macrophages
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spelling Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammationMalandrino, Maria IdaFucho Salvador, RaquelWeber Blattes, MinéiaCalderón Domínguez, MaríaMir Bonnín, Joan FrancescValcarcel-Jimenez, LoreaEscoté, XavierGómez-Serrano, MaríaPeral, BelénSalvadó Serra, LaiaCasals i Farré, NúriaVillarroya i Gombau, FrancescVázquez Carrera, ManuelVendrell, JoanSerra i Cucurull, DolorsHerrero Rodríguez, LauraObesitatDiabetis no-insulinodependentÀcids grassosInflamacióMacròfagsObesityNon-insulin-dependent diabetesFatty acidsInflammationMacrophagesLipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.American Physiological Society2015201720152015info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion51 p.application/pdfhttps://hdl.handle.net/2445/65775Articles 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)Ingléshttp://dx.doi.org/10.1152/ajpendo.00362.2014American Journal of Physiology-Endocrinology and Metabolism, 2015, vol. 308, num. 9, p. E756-E769http://dx.doi.org/10.1152/ajpendo.00362.2014info:eu-repo/grantAgreement/EC/FP7/277713(c) American Physiological Society, 2015info:eu-repo/semantics/openAccessoai:recercat.cat:2445/657752026-05-29T05:05:01Z
dc.title.none.fl_str_mv Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation
title Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation
spellingShingle Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation
Malandrino, Maria Ida
Obesitat
Diabetis no-insulinodependent
Àcids grassos
Inflamació
Macròfags
Obesity
Non-insulin-dependent diabetes
Fatty acids
Inflammation
Macrophages
title_short Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation
title_full Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation
title_fullStr Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation
title_full_unstemmed Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation
title_sort Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation
dc.creator.none.fl_str_mv Malandrino, Maria Ida
Fucho Salvador, Raquel
Weber Blattes, Minéia
Calderón Domínguez, María
Mir Bonnín, Joan Francesc
Valcarcel-Jimenez, Lorea
Escoté, Xavier
Gómez-Serrano, María
Peral, Belén
Salvadó Serra, Laia
Casals i Farré, Núria
Villarroya i Gombau, Francesc
Vázquez Carrera, Manuel
Vendrell, Joan
Serra i Cucurull, Dolors
Herrero Rodríguez, Laura
author Malandrino, Maria Ida
author_facet Malandrino, Maria Ida
Fucho Salvador, Raquel
Weber Blattes, Minéia
Calderón Domínguez, María
Mir Bonnín, Joan Francesc
Valcarcel-Jimenez, Lorea
Escoté, Xavier
Gómez-Serrano, María
Peral, Belén
Salvadó Serra, Laia
Casals i Farré, Núria
Villarroya i Gombau, Francesc
Vázquez Carrera, Manuel
Vendrell, Joan
Serra i Cucurull, Dolors
Herrero Rodríguez, Laura
author_role author
author2 Fucho Salvador, Raquel
Weber Blattes, Minéia
Calderón Domínguez, María
Mir Bonnín, Joan Francesc
Valcarcel-Jimenez, Lorea
Escoté, Xavier
Gómez-Serrano, María
Peral, Belén
Salvadó Serra, Laia
Casals i Farré, Núria
Villarroya i Gombau, Francesc
Vázquez Carrera, Manuel
Vendrell, Joan
Serra i Cucurull, Dolors
Herrero Rodríguez, Laura
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Obesitat
Diabetis no-insulinodependent
Àcids grassos
Inflamació
Macròfags
Obesity
Non-insulin-dependent diabetes
Fatty acids
Inflammation
Macrophages
topic Obesitat
Diabetis no-insulinodependent
Àcids grassos
Inflamació
Macròfags
Obesity
Non-insulin-dependent diabetes
Fatty acids
Inflammation
Macrophages
description Lipid overload in obesity and type 2 diabetes is associated with adipocyte dysfunction, inflammation, macrophage infiltration, and decreased fatty acid oxidation (FAO). Here, we report that the expression of carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme in mitochondrial FAO, is higher in human adipose tissue macrophages than in adipocytes and that it is differentially expressed in visceral vs. subcutaneous adipose tissue in both an obese and a type 2 diabetes cohort. These observations led us to further investigate the potential role of CPT1A in adipocytes and macrophages. We expressed CPT1AM, a permanently active mutant form of CPT1A, in 3T3-L1 CARΔ1 adipocytes and RAW 264.7 macrophages through adenoviral infection. Enhanced FAO in palmitate-incubated adipocytes and macrophages reduced triglyceride content and inflammation, improved insulin sensitivity in adipocytes, and reduced endoplasmic reticulum stress and ROS damage in macrophages. We conclude that increasing FAO in adipocytes and macrophages improves palmitate-induced derangements. This indicates that enhancing FAO in metabolically relevant cells such as adipocytes and macrophages may be a promising strategy for the treatment of chronic inflammatory pathologies such as obesity and type 2 diabetes.
publishDate 2015
dc.date.none.fl_str_mv 2015
2015
2015
2017
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/65775
url https://hdl.handle.net/2445/65775
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv http://dx.doi.org/10.1152/ajpendo.00362.2014
American Journal of Physiology-Endocrinology and Metabolism, 2015, vol. 308, num. 9, p. E756-E769
http://dx.doi.org/10.1152/ajpendo.00362.2014
info:eu-repo/grantAgreement/EC/FP7/277713
dc.rights.none.fl_str_mv (c) American Physiological Society, 2015
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) American Physiological Society, 2015
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 51 p.
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869416664746950656
score 15.811543

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