PloS one, 2015-12, Vol.10 (12), p.e0145244-e0145244
- Arrabal, Sergio
- Lucena, Miguel Angel
- Canduela, Miren Josune
- Ramos-Uriarte, Almudena
- Rivera, Patricia
- Serrano, Antonia
- Pavón, Francisco Javier
- Decara, Juan
- Vargas, Antonio
- Baixeras, Elena
- Martín-Rufián, Mercedes
- Márquez, Javier
- Fernández-Llébrez, Pedro
- De Roos, Baukje
- Grandes, Pedro
- Rodríguez de Fonseca, Fernando
- Suárez, Juan
- Appanna, Vasu D.
2015
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- Autor(en) / Beteiligte
- Arrabal, Sergio
- Lucena, Miguel Angel
- Canduela, Miren Josune
- Ramos-Uriarte, Almudena
- Rivera, Patricia
- Serrano, Antonia
- Pavón, Francisco Javier
- Decara, Juan
- Vargas, Antonio
- Baixeras, Elena
- Martín-Rufián, Mercedes
- Márquez, Javier
- Fernández-Llébrez, Pedro
- De Roos, Baukje
- Grandes, Pedro
- Rodríguez de Fonseca, Fernando
- Suárez, Juan
- Appanna, Vasu D.
- Titel
- Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle
- Ist Teil von
- PloS one, 2015-12, Vol.10 (12), p.e0145244-e0145244
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2015
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Cannabinoid 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0145244Titel-ID: cdi_plos_journals_1757043563
- Format
- –
- Schlagworte
- Animals, Bioenergetics, Biosynthesis, Body weight, Body Weight - drug effects, Cannabinoid CB1 receptors, Carbohydrates, Cell Line, Dehydrogenase, Dehydrogenases, Diabetes, Diet, Dietary Carbohydrates, Dihydrolipoamide Dehydrogenase - genetics, Dihydrolipoamide Dehydrogenase - metabolism, Down-regulation, Electrophoresis, Gel, Two-Dimensional, Energy, Energy metabolism, Enzymes, Feeding Behavior - drug effects, Food intake, Gene expression, Gene Expression Regulation - drug effects, Glucose, Glucose - metabolism, Glucose isomerase, Glutathione, Glutathione reductase, Glutathione Reductase - metabolism, Glycolysis, Homeostasis, Insulin resistance, L-Lactate dehydrogenase, Lactate dehydrogenase, Lactic acid, Male, Mass spectrometry, Mass spectroscopy, Metabolism, Mice, Inbred C57BL, Mitochondria, Mitochondria - drug effects, Mitochondria - enzymology, Muscle Fibers, Skeletal - drug effects, Muscle Fibers, Skeletal - enzymology, Muscles, Muscles - drug effects, Muscles - enzymology, Myotubes, Neurosciences, Obesity, Obesity - enzymology, Obesity - genetics, Obesity - metabolism, Overexpression, Oxidation, Oxidation-Reduction - drug effects, Pharmacology, Phosphates, Phosphopyruvate hydratase, Piperidines - pharmacology, Pyrazoles - pharmacology, Pyruvaldehyde, Pyruvic acid, Pyruvic Acid - metabolism, Rats, Wistar, Receptor, Cannabinoid, CB1 - metabolism, Receptors, Rodents, Spectrometry, Mass, Electrospray Ionization, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tricarboxylic acid cycle, Triose-phosphate isomerase, Weight control