Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/2333
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dc.contributor.authorArrabal, Sergio-
dc.contributor.authorLucena, Miguel Angel-
dc.contributor.authorCanduela, Miren Josune-
dc.contributor.authorRamos-Uriarte, Almudena-
dc.contributor.authorRivera, Patricia-
dc.contributor.authorSerrano, Antonia-
dc.contributor.authorPavón, Francisco Javier-
dc.contributor.authorDecara, Juan-
dc.contributor.authorVargas, Antonio-
dc.contributor.authorBaixeras, Elena-
dc.contributor.authorMartín-Rufián, Mercedes-
dc.contributor.authorMárquez, Javier-
dc.contributor.authorFernández-Llébrez, Pedro-
dc.contributor.authorDe Roos, Baukje-
dc.contributor.authorGrandes, Pedro-
dc.contributor.authorRodríguez de Fonseca, Fernando-
dc.contributor.authorSuárez, Juan-
dc.date.accessioned2016-08-09T08:55:34Z-
dc.date.available2016-08-09T08:55:34Z-
dc.date.issued2015-12-15-
dc.identifier.citationArrabal S, Lucena MA, Canduela MJ, Ramos-Uriarte A, Rivera P, Serrano A, et al. Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle. PLoS ONE. 2015; 10(12):e0145244es
dc.identifier.issn1932-6203 (Online)-
dc.identifier.otherPMC4682857-
dc.identifier.urihttp://hdl.handle.net/10668/2333-
dc.descriptionJournal Article; Research Support, Non-U.S. Gov't;es
dc.description.abstractCannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of α-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg(-1), 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle--regulated by both diet and CB1 receptor activity--through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD.es
dc.description.sponsorshipThis work was supported by CIBERobn (CB06/03/1008), Ministerio de Economía y Competitividad (MINECO) (PG: BFU2012-33334), Instituto de Salud Carlos III (ISCIII), MINECO, co-funded by UE-ERDF program (JS: CP12/03109), Red de Trastornos Adictivos (FRF: RD12/0028/0001, PG: RD12/0028/0004, JM: RD12/0028/0013), The Basque Country Government (PG: BCG IT764-13), Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE-ERDF (FRF: CTS-8221, JM: CVI-6656), Consejería de Salud, Junta de Andalucía, UE-ERDF (FRF: SAS111224), and University of the Basque Country UPV/EHU (PG: UFI11/41). JS, FJP and AS hold “Miguel Servet” research contracts from the National System of Health, ISCIII, UE-ERDF (CP12/03109, CP14/00212, and CP14/00173 respectively).es
dc.language.isoenes
dc.publisherPublic Library of Sciencees
dc.relation.ispartofPloS onees
dc.subjectMúsculos abdominaleses
dc.subjectPeso corporales
dc.subjectCannabinoideses
dc.subjectMetabolismo energéticoes
dc.subjectGlucosaes
dc.subjectRatases
dc.subjectObesidades
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on Aldehyde or Oxo Group Donors::Ketone Oxidoreductases::3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)es
dc.subject.meshMedical Subject Headings::Anatomy::Musculoskeletal System::Muscles::Muscle, Skeletal::Abdominal Muscleses
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animalses
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Anthropometry::Body Weights and Measures::Body Size::Body Weightes
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoidses
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Dietes
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Flavoproteins::Dihydrolipoamide Dehydrogenasees
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Down-Regulationes
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Electrochemical Techniques::Electrophoresises
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Energy Metabolismes
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Flavoproteinses
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucosees
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Oxidoreductases Acting on Sulfur Group Donors::Glutathione Reductasees
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Oxidoreductases::Alcohol Oxidoreductases::Lactate Dehydrogenases::L-Lactate Dehydrogenasees
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Hydroxy Acids::Lactateses
dc.subject.meshMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Micees
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondriaes
dc.subject.meshMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Mitochondria::Mitochondria, Musclees
dc.subject.meshMedical Subject Headings::Anatomy::Tissues::Muscles::Muscle, Striated::Muscle, Skeletal::Muscle Fibers, Skeletales
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Physical Examination::Body Constitution::Body Weights and Measures::Body Size::Body Weight::Overweight::Obesityes
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Inorganic Chemicals::Phosphorus Compounds::Phosphorus Acids::Phosphoric Acids::Phosphateses
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Lyases::Carbon-Oxygen Lyases::Hydro-Lyases::Phosphopyruvate Hydratasees
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Piperidineses
dc.subject.meshMedical Subject Headings::Disciplines and Occupations::Natural Science Disciplines::Chemistry::Biochemistry::Proteomicses
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Azoles::Pyrazoleses
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Aldehydes::Glyoxal::Pyruvaldehydees
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1es
dc.subject.meshMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Mass Spectrometry::Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionizationes
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Tricarboxylic Acidses
dc.subject.meshMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Isomerases::Intramolecular Oxidoreductases::Aldose-Ketose Isomerases::Triose-Phosphate Isomerasees
dc.subject.meshMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Chemical Processes::Biochemical Processes::Up-Regulationes
dc.titlePharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle.es
dc.typeinfo:eu-repo/semantics/articlees
dc.description.versionYeses
dc.identifier.pmid26671069-
dc.rights.accessRightsAcceso abiertoes
dc.identifier.doi10.1371/journal.pone.0145244-
dc.type.versioninfo:eu-repo/semantics/publishedes
dc.relation.publisherversionhttp://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145244es
dc.contributor.authoraffiliation[Arrabal,S; Lucena, MA; Rivera, P; Serrano,A; Pavón, FJ, Decara,J; Vargas,A; Baixeras,E; Rodriguez de Fonseca,F; Suárez,J] UGC Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA). Universidad de Málaga. Hospital Universitario Regional de Málaga, Málaga, Spain. [Arrabal,S; Rivera, P; Serrano,A; Pavón, FJ, Decara,J; Vargas,A; Baixeras,E; Rodriguez de Fonseca,F; Suárez,J] CIBEROBN, Instituto de Salud Carlos III, Madrid, Spain. [Canduela,MJ; Ramos-Uriarte,A; Grandes,P] Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa, Spain. [Martín-Rufián,M] ECAI de Proteómica, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Márquez,J] Departamento de Biología Molecular y Bioquímica, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Fernández-Llébrez,P] Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [De Roos,B] University of Aberdeen, Rowett Institute of Nutrition & Health, Aberdeen, United Kingdom.es
dc.type.subtypeArtículoes
Appears in Collections:01- Artículos - IBIMA. Instituto de Investigación Biomédica de Málaga
01- Artículos - Hospital Regional de Málaga

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