RESUMEN
This study investigated the effects of high-fat (HF) diet on parameters of oxidative stress among muscles with distinct fiber type composition and oxidative capacities. To accomplish that, male Wistar rats were fed either a low-fat standard chow (SC) or a HF diet for 8 weeks. Soleus, extensor digitorum longus (EDL), and epitrochlearis muscles were collected and mitochondrial H2O2 (mtH2O2) emission, palmitate oxidation, and gene expression and antioxidant system were measured. Chronic HF feeding enhanced fat oxidation in oxidative and glycolytic muscles. It also caused a significant reduction in mtH2O2 emission in the EDL muscle, although a tendency towards a reduction was also found in the soleus and epitrochlearis muscles. In the epitrochlearis, HF diet increased mRNA expression of the NADPH oxidase complex; however, this muscle also showed an increase in the expression of antioxidant proteins, suggesting a higher capacity to generate and buffer ROS. The soleus muscle, despite being highly oxidative, elicited H2O2 emission rates equivalent to only 20% and 35% of the values obtained for EDL and epitrochlearis muscles, respectively. Furthermore, the Epi muscle with the lowest oxidative capacity was the second highest in H2O2 emission. In conclusion, it appears that intrinsic differences related to the distribution of type I and type II fibers, rather than oxidative capacity, drove the activity of the anti- and pro-oxidant systems and determine ROS production in different skeletal muscles. This also suggests that the impact of potentially deleterious effects of ROS production on skeletal muscle metabolism/function under lipotoxic conditions is fiber type-specific.
Asunto(s)
Dieta Alta en Grasa/efectos adversos , Mitocondrias/metabolismo , Fibras Musculares Esqueléticas/metabolismo , NADPH Oxidasas/genética , Obesidad/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Animales , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Masculino , Mitocondrias/patología , Proteínas Desacopladoras Mitocondriales/genética , Proteínas Desacopladoras Mitocondriales/metabolismo , Contracción Muscular/fisiología , Fibras Musculares Esqueléticas/clasificación , Fibras Musculares Esqueléticas/patología , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , NADPH Oxidasas/metabolismo , Obesidad/etiología , Obesidad/patología , Especificidad de Órganos , Oxidación-Reducción , Estrés Oxidativo , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo , Ratas , Ratas WistarRESUMEN
Oxfenicine is a carnitine-palmitoyl transferase 1b (CPT-1b)-specific inhibitor that has been shown to improve whole body insulin sensitivity while suppressing fatty acid (FA) oxidation and increasing circulating FA. Because the white adipose tissue (WAT) is an organ that stores and releases FAs, this study investigated whether oxfenicine-induced inhibition of FA oxidation affected adiposity and WAT metabolism in rats fed either low (LF) or high-fat (HF) diets. Following 8 wk of dietary intervention, male Sprague-Dawley rats were given a daily intraperitoneal injection of oxfenicine (150 mg/kg body wt) or vehicle (PBS) for 3 wk. Oxfenicine treatment reduced whole body fat oxidation, body weight, and adiposity, and improved insulin sensitivity in HF-fed rats. All of these effects occurred without alterations in food intake, energy expenditure, and ambulatory activity. In vivo oxfenicine treatment reduced FA oxidation and lipolysis in subcutaneous inguinal (SC Ing) adipocytes, whereas glucose incorporation into lipids (lipogenesis) was significantly reduced in both SC Ing and epididymal (Epid) adipocytes. In summary, our results show that oxfenicine-induced inhibition of CPT-1b markedly affects WAT metabolism, leading to reduced adiposity through a mechanism that involves reduced lipogenesis in the SC Ing and Epid fat depots of rats.
Asunto(s)
Tejido Adiposo Blanco/diagnóstico por imagen , Tejido Adiposo Blanco/fisiología , Adiposidad/fisiología , Carnitina O-Palmitoiltransferasa/antagonistas & inhibidores , Carnitina O-Palmitoiltransferasa/metabolismo , Glicina/análogos & derivados , Lipogénesis/fisiología , Lipólisis/fisiología , Adiposidad/efectos de los fármacos , Animales , Inhibidores Enzimáticos/farmacología , Glicina/farmacología , Lipogénesis/efectos de los fármacos , Lipólisis/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
This study investigated the regulation of thermogenic capacity in classical brown adipose tissue (BAT) and subcutaneous inguinal (SC Ing) white adipose tissue (WAT) and how it affects whole-body energy expenditure in sedentary and endurance-trained rats fed ad libitum either low fat or high fat (HF) diets. Analysis of tissue mass, PGC-1α and UCP-1 content, the presence of multilocular adipocytes, and palmitate oxidation revealed that a HF diet increased the thermogenic capacity of the interscapular and aortic brown adipose tissues, whereas exercise markedly suppressed it. Conversely, exercise induced browning of the SC Ing WAT. This effect was attenuated by a HF diet. Endurance training neither affected skeletal muscle FNDC5 content nor circulating irisin, but it increased FNDC5 content in SC Ing WAT. This suggests that locally produced FNDC5 rather than circulating irisin mediated the exercise-induced browning effect on this fat tissue. Importantly, despite reducing the thermogenic capacity of classical BAT, exercise increased whole-body energy expenditure during the dark cycle. Therefore, browning of subcutaneous WAT likely exerted a compensatory effect and raised whole-body energy expenditure in endurance-trained rats. Based on these novel findings, we propose that exercise-induced browning of the subcutaneous WAT provides an alternative mechanism that reduces thermogenic capacity in core areas and increases it in peripheral body regions. This could allow the organism to adjust its metabolic rate to accommodate diet-induced thermogenesis while simultaneously coping with the stress of chronically increased heat production through exercise.