Muscle Physiology Changes Induced by Every Other Day Feeding and Endurance Exercise in Mice: Effects on Physical Performance

Every other day feeding (EOD) and exercise induce changes in cell metabolism. The aim of the present work was to know if both EOD and exercise produce similar effects on physical capacity, studying their physiological, biochemical and metabolic effects on muscle. Male OF-1 mice were fed either ad libitum (AL) or under EOD. After 18 weeks under EOD, animals were also trained by using a treadmill for another 6 weeks and then analyzed for physical activity. Both, EOD and endurance exercise increased the resistance of animals to extenuating activity and improved motor coordination. Among the groups that showed the highest performance, AL and EOD trained animals, ALT and EODT respectively, only the EODT group was able to increase glucose and triglycerides levels in plasma after extenuating exercise. No high effects on mitochondrial respiratory chain activities or protein levels neither on coenzyme Q levels were found in gastrocnemius muscle. However, exercise and EOD did increase β-oxidation activity in this muscle accompanied by increased CD36 levels in animals fed under EOD and by changes in shape and localization of mitochondria in muscle fibers. Furthermore, EOD and training decreased muscle damage after strenuous exercise. EOD also reduced the levels of lipid peroxidation in muscle. Our results indicate that EOD improves muscle performance and resistance by increasing lipid catabolism in muscle mitochondria at the same time that prevents lipid peroxidation and muscle damage

Epigenetics in aging and age-related diseases

7 páginas.Peer reviewe

Resveratrol-induce s-phase delay in cell cycle depends on cell metabolism

Resumen del póster presentado al XIV Congresos de la Sociedad Española de Biología Celular, celebrado en Málaga del 12 al 15 de diciembre de 2011.The effect of polyphenols in cell cycle progression of tumor cell lines is widely known. Among polyphenols, resveratrol (RSV) is a stilbenoid known to activate sirtuins and to show prolongevity effects (Baur et al., 2006). Treatment of tumor cell lines with RSV produces a dose-dependent S-phase delay starting as early as 6-12 hours of incubation. Cell cycle distribution seems to return to normal values with time and depends on the dose of RSV. This delay occurs in both cell lines expressing and lacking p53. However, in cell lines able to express p53, RSV increases its protein levels and also the levels of downstream targets such as p21. Although RSV is considered an antioxidant, treatment of HeLa cells with this compound increases ROS levels in a time and dose-dependent mechanism. Other polyphenols such as dicumarol also increase ROS levels and induce S-phase delay (Hernández et al, 2008). However, incubation of RSV-treated cells with antioxidants and superoxide dismutase mimetics did not block S-phase delay induced by this polyphenol. On the other hand, RSV has been shown to increase AMPK activity. Incubation of HeLa cells with an AiCAR, an AMPK ligand, induced S-phase delay in a similar way as RSV. In order to determine if AMPK activity is related to S-phase delay, we preincubated cells with an inhibitor of AMPK and further treated them with RSV. Unfortunately, the inhibitor was unable to block RSV-dependent Sphase delay. Further, A549 cells, that do not express LKB1, a necessary upstream regulator of AMPK, also suffered S-phase delay after RSV treatment indicating that AMPK seems to be not involved. Tumor cells show a more glycolitic metabolism whereas primary cell lines are more respiratory. MEFs were more resistant to RSV-induced cell cycle delay than HeLa or other tumor cells. We conditioned HeLa cells to grow under low glucose conditions (1 g/l). These cells showed a more respiratory metabolism in comparison with their counterparts cultured under high glucose conditions and also showed a higher resistance against RSV. Taken together, our results indicate that metabolic profile of cells is a key factor in RSV-induced cell cycle delay.Peer reviewe

Resveratrol in cancer: cellular and mitochondrial consequences of proton transport inhibition

Transformed cells suffer several changes leading to the increase of protective mechanisms and show a metabolic profile in accordance with higher proliferative capacity. In these mechanisms, changes in mitochondrial activity cause a higher glycolytic metabolism in detriment of oxidative phosphorylation. In these changes, H +-ATPase regulation seems to be importantly involved. During the last years, polyphenols and specially the stilbene resveratrol and related members of its family have been studied because they are able to affect tumour cell growth and cancer progression. Among the different effects induced by resveratrol, inhibition of H +-ATPase seems to be one important mechanism in its effect on cancer progression. Further, an ectopic H +-ATPase located in the outer surface of plasma membrane has been recently involved in cancer progression and angiogenesis. In this article we review the latest findings about resveratrol inhibition of H +-ATPase and its importance in tumour cell growth and cancer progression.Peer Reviewe

Efecto del resveratrol en la progresión del ciclo celular: papel principal del cambio metabólico y reversión del efecto Warburg

Resumen del póster presentado al XXXIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular celebrado en Córdoba del 14 al 17 de septiembre de 2010.Las células tumorales se caracterizan por presentar un metabolismo anaeróbico ya que debido a su rápido crecimiento se desarrollan en ambientes hipóxicos. Este fenómeno fue descrito en 1920 por Otto Warburg, quién demostró que las células cancerosas obtenían el ATP principalmente por fermentación. El resveratrol (RSV) es un polifenol de la familia de los estibenoides que se sintetiza en gran variedad de plantas en respuesta a infecciones fúngicas y condiciones adversas como la radiación ultravioleta y la temperatura. El RSV, además de una molécula antioxidante es también ampliamente conocido como un agente activador de SIRT1, proteína deacetilasa dependiente de NAD+. Nosotros hemos demostrado que RSV induce, de forma dosisdependiente, una parada en fase S en todos tipos celulares testados como HeLa, HL-60, HTC116 y CHO. Nuestra hipótesis caracteriza al resveratrol como una molécula capaz de inducir un retraso en la progresión del ciclo celular, debido a que provoca un cambio metabólico que hace a las células tumorales realicen un metabolismo oxidativo, mediante el incremento en los niveles de determinadas enzimas como la PDH, TIGAR y p53 , entre otras. En este proceso parece que la activación de SIRT1 no es el mecanismo por el que el resveratrol produce la transición de metabolismo anaeróbico a aeróbico. Esta transición es clave para que se produzca el retraso en la fase S del ciclo celular. Proponemos que el resveratrol, posiblemente a través de la activación de p53, podría estar activando la respiración mitocondrial, creando así una célula más susceptible a determinados tratamientos antitumorales.Peer reviewe

Metabolic changes induced by resveratrol in tumoral cells

Resumen del póster presentado al 22nd IUBMB & 37th FEBS Congress, celebrado en Sevilla (España) del 4 al 9 de septiembre de 2012.Resveratrol (RSV) is a stilbenoid known to activate sirtuins and to show prolongevity effects (Baur et al., 2006). It is known that the treatment of tumor cell lines with RSV produces a dosedependent S-phase delay starting as early as 6-12 hours of incubation. Cell cycle distribution seems to return to normal values after 48 hour of treatment depending on the dose of RSV. After this delay, metabolism of tumoral cells has passed from glycolitic to more respiratory metabolism. We have previously shown that RSV increases mitochondrial mass in several cell types including tumoral cells such as the human epithelial cervical cancer cell line HeLa (Baur et al., 2006). RSV increased oxygen consumption in glycolitic HeLa cells accompanied by the modification of the activity and protein levels of electron transport chain components. Further, RSV induced a significant increase in b-oxidation. This effect was accompanied by increases in b-oxidation-related protein levels such as CPT-1 and CPT-2. Further, RSV also modified levels of pyridine nucleotides in cells by decreasing the ratio NADH/NAD+. Although RSV is considered an antioxidant, treatment of HeLa cells with this compound increases ROS levels in a time and dose-dependent mechanism. This increase in ROS levels was produced in parallel of changed found in mitochondria. All this process was accompanied by the induction of autophagic mechanisms as determined by the increase in autophagy protein levels such as Beclin-1 or ATG-3. Our results indicate that RSV affects cell cycle progression at the same time that it is modifying the metabolism of tumoral cells from glycolysis to respiration. In this process, mitochondrial remodeling by induction of biogenesis at the same time than autophagy is involved. Baur et al. Nature 2007;444(7117):337-342.Peer Reviewe

Resveratrol: an ergogenic compound

7 páginas, 1 figura.Human sedentary lifestyle is the main responsible of the increase of the risk for cardiovascular diseases, diabetes, obesity and other metabolic diseases. Then, it is very important to find some alternative therapies based on exercise, balanced and calorie controlled diets and supplementation with bioactive compounds including those with antioxidant properties to ameliorate the life expectancy and improve the capacity of people affected for these diseases or elderly people. In the present work we show the molecular and cellular similarities between the mechanism of action of exercise, caloric restriction and polyphenols on muscle performance. Thus, therapies based on diet, exercise and dietary supplements can increase muscle capacity during aging decreasing the dependency of the individuals during later years in human life. We propose here that healthier lifestyle based on moderate exercise and an equilibrated diet together with the use of natural ergogenic compounds can be the key factors for healthy aging and the therapy for cardiovascular and metabolic diseases.This work has been supported by the Spanish Ministerio de Educación y Ciencia grant DEP2005-00238-C04-04Peer reviewe