title: Carnitine Palmitoyltransferase 1 Increases Lipolysis, UCP1 Protein Expression and Mitochondrial Activity in Brown Adipocytes.
abstract: The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders.
authors.affiliation: Department of Biochemistry and Physiology, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Calderon-Dominguez
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona) and Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, E-08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sebastián
authors.affiliation: Department of Biochemistry and Physiology, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Fucho
authors.affiliation: Department of Biochemistry and Physiology, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
authors.forename: Minéia
authors.initials: M
authors.lastname: Weber
authors.affiliation: Department of Biochemistry and Physiology, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
authors.forename: Joan F
authors.initials: JF
authors.lastname: Mir
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) and Instituto de Investigación Sanitaria La Paz, 28029, Madrid, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: García-Casarrubios
authors.affiliation: Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) and Instituto de Investigación Sanitaria La Paz, 28029, Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Obregón
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona) and Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, E-08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zorzano
authors.affiliation: Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Instituto de Salud Carlos III, E-28029, Madrid, Spain.|Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) and Instituto de Investigación Sanitaria La Paz, 28029, Madrid, Spain.
authors.forename: Ángela M
authors.initials: ÁM
authors.lastname: Valverde
authors.affiliation: Department of Biochemistry and Physiology, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
authors.forename: Dolors
authors.initials: D
authors.lastname: Serra
authors.affiliation: Department of Biochemistry and Physiology, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, E-08028, Barcelona, Spain.|Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, E-28029, Madrid, Spain.
authors.forename: Laura
authors.identifier: http://orcid.org/0000-0003-4244-4673
authors.initials: L
authors.lastname: Herrero
mesh_terms: D052437:Adipocytes, Brown / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002334:Carnitine O-Palmitoyltransferase / Q000096:biosynthesis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D004734:Energy Metabolism / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000235:genetics; D008066:Lipolysis / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D022722:Thermogenesis / Q000235:genetics; D000071256:Uncoupling Protein 1 / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D008055:Lipids; C000604371:UCP1 protein, human; D000071256:Uncoupling Protein 1; D002334:Carnitine O-Palmitoyltransferase