RESUMEN
Beta-Guanadinopropionic acid (beta-GPA) feeding leads to reductions in skeletal muscle phosphagen concentrations and has been used as a tool with which to study the effects of energy charge on skeletal muscle metabolism. Supplementing standard rodent diets with beta-GPA leads to increases in mitochondrial enzyme content in fast but not slow-twitch muscles from male rats. Given this apparent discrepancy between muscle types we used beta-GPA feeding as a model to study signaling pathways involved in mitochondrial biogenesis. We hypothesized that beta-GPA feeding would result in a preferential activation of p38 MAPK and AMPK signaling and reductions in RIP140 protein content in triceps but not soleus muscle. Despite similar reductions in high-energy phosphate concentrations, 6 wk of beta-GPA feeding led to increases in mitochondrial proteins in triceps but not soleus muscles. Differences in the response of mitochondrial proteins to beta-GPA feeding did not seem to be related to a differential activation of p38 MAPK and AMPK signaling pathways or discrepancies in the induction of PPARgamma coactivator (PGC)-1alpha and -1beta. The protein content and expression of the nuclear corepressor RIP140 was reduced in triceps but not soleus muscle. Collectively our results indicate that chronic reductions in high-energy phosphates lead to the activation of p38 MAPK and AMPK signaling and increases in the expression of PGC-1alpha and -1beta in both soleus and triceps muscles. The lack of an effect of beta-GPA feeding on mitochondrial proteins in the soleus muscles could be related to a fiber type-specific effect of beta-GPA on RIP140 protein content.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adenilato Quinasa/metabolismo , Guanidinas/farmacología , Músculo Esquelético/citología , Músculo Esquelético/enzimología , Proteínas Nucleares/metabolismo , Propionatos/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Alimentación Animal , Animales , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , ADN Mitocondrial/genética , Metabolismo Energético/efectos de los fármacos , Metabolismo Energético/fisiología , Masculino , Proteínas Mitocondriales/genética , Proteínas Mitocondriales/metabolismo , Fibras Musculares de Contracción Rápida/efectos de los fármacos , Fibras Musculares de Contracción Rápida/enzimología , Fibras Musculares de Contracción Lenta/efectos de los fármacos , Fibras Musculares de Contracción Lenta/enzimología , Proteínas Nucleares/genética , Proteína de Interacción con Receptores Nucleares 1 , PPAR gamma/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
The purpose of the present investigation was to explore the effects of exercise and adrenaline on the mRNA expression of PGC-1alpha, a master regulator of mitochondrial biogenesis, in rat abdominal adipose tissue. We hypothesized that (1) exercise training would increase PGC-1alpha mRNA expression in association with increases in mitochondrial marker enzymes, (2) adrenaline would increase PGC-1alpha mRNA expression and (3) the effect of exercise on PGC-1alpha mRNA expression in white adipose tissue would be attenuated by a beta-blocker. Two hours of daily swim training for 4 weeks led to increases in mitochondrial marker proteins and PGC-1alpha mRNA expression in epididymal and retroperitoneal fat depots. Additionally, a single 2 h bout of exercise led to increases in PGC-1alpha mRNA expression immediately following exercise cessation. Adrenaline treatment of adipose tissue organ cultures led to dose-dependent increases in PGC-1alpha mRNA expression. A supra-physiological concentration of adrenaline increased PGC-1alpha mRNA expression in epididymal but not retroperitoneal adipose tissue. beta-Blockade attenuated the effects of an acute bout of exercise on PGC-1alpha mRNA expression in epididymal but not retroperitoneal fat pads. In summary, this is the first investigation to demonstrate that exercise training, an acute bout of exercise and adrenaline all increase PGC-1alpha mRNA expression in rat white adipose tissue. Furthermore it would appear that increases in circulating catecholamine levels may be one potential mechanism mediating exercise induced increases in PGC-1alpha mRNA expression in rat abdominal adipose tissue.
