RT Journal Article
T1 Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle.
A1 Arrabal, Sergio
A1 Lucena, Miguel Angel
A1 Canduela, Miren Josune
A1 Ramos-Uriarte, Almudena
A1 Rivera, Patricia
A1 Serrano, Antonia
A1 Pavón, Francisco Javier
A1 Decara, Juan
A1 Vargas, Antonio
A1 Baixeras, Elena
A1 Martín-Rufián, Mercedes
A1 Márquez, Javier
A1 Fernández-Llébrez, Pedro
A1 De Roos, Baukje
A1 Grandes, Pedro
A1 Rodríguez de Fonseca, Fernando
A1 Suárez, Juan
K1 Músculos abdominales
K1 Peso corporal
K1 Cannabinoides
K1 Metabolismo energético
K1 Glucosa
K1 Ratas
K1 Obesidad
AB 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.
PB Public Library of Science
YR 2015
FD 2015-12-15
LK http://hdl.handle.net/10668/2333
UL http://hdl.handle.net/10668/2333
LA en
NO Arrabal 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):e0145244
NO Journal Article; Research Support, Non-U.S. Gov't;
DS RISalud
RD Apr 8, 2025