title: Enhanced fatty acid oxidation in adipocytes and macrophages reduces lipid-induced triglyceride accumulation and inflammation.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Maria Ida
authors.initials: MI
authors.lastname: Malandrino
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Raquel
authors.initials: R
authors.lastname: Fucho
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Minéia
authors.initials: M
authors.lastname: Weber
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: María
authors.initials: M
authors.lastname: Calderon-Dominguez
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Joan Francesc
authors.initials: JF
authors.lastname: Mir
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Lorea
authors.initials: L
authors.lastname: Valcarcel
authors.affiliation: Endocrinology and Diabetes Unit, Joan XXIII University Hospital, Institut d'Investigació Sanitària Pere i Virgili, Universitat Rovira i Virgili, Tarragona, Spain; Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Xavier
authors.initials: X
authors.lastname: Escoté
authors.affiliation: Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain;
authors.forename: María
authors.initials: M
authors.lastname: Gómez-Serrano
authors.affiliation: Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Madrid, Spain;
authors.forename: Belén
authors.initials: B
authors.lastname: Peral
authors.affiliation: Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain; Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry and Institut de Biomedicina de la Universitat de Barcelona, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; and.
authors.forename: Laia
authors.initials: L
authors.lastname: Salvadó
authors.affiliation: Endocrinology and Diabetes Unit, Joan XXIII University Hospital, Institut d'Investigació Sanitària Pere i Virgili, Universitat Rovira i Virgili, Tarragona, Spain; Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Sonia
authors.initials: S
authors.lastname: Fernández-Veledo
authors.affiliation: Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain; Basic Sciences Department, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Casals
authors.affiliation: Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain; Pharmacology Unit, Department of Pharmacology and Therapeutic Chemistry and Institut de Biomedicina de la Universitat de Barcelona, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain; and.
authors.forename: Manuel
authors.initials: M
authors.lastname: Vázquez-Carrera
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Francesc
authors.initials: F
authors.lastname: Villarroya
authors.affiliation: Endocrinology and Diabetes Unit, Joan XXIII University Hospital, Institut d'Investigació Sanitària Pere i Virgili, Universitat Rovira i Virgili, Tarragona, Spain; Institut de Biomedicina de la Universitat de Barcelona de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Joan J
authors.initials: JJ
authors.lastname: Vendrell
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
authors.forename: Dolors
authors.initials: D
authors.lastname: Serra
authors.affiliation: Department of Biochemistry and Molecular Biology, Institut de Biomedicina de la Universitat de Barcelona, Universitat de Barcelona, Barcelona, Spain; Institut de Biomedicina de la Universitat de Barcelona Fisiopatología de la Obesidad y la Nutrición, Instituto de Salud Carlos III, Madrid, Spain; lherrero@ub.edu.
authors.forename: Laura
authors.initials: L
authors.lastname: Herrero
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000818:Animals; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism; D010084:Oxidation-Reduction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D008055:Lipids; D014280:Triglycerides
keywords: CPT1; adipocytes; fatty acid oxidation; inflammation; macrophages; obesity; type 2 diabetes