ABSTRACT
Skeletal muscles are composed of hundreds of multinucleated muscle fibers (myofibers) whose myonuclei are regularly positioned all along the myofiber's periphery except the few ones clustered underneath the neuromuscular junction (NMJ) at the synaptic zone. This precise myonuclei organization is altered in different types of muscle disease, including centronuclear myopathies (CNMs). However, the molecular machinery regulating myonuclei position and organization in mature myofibers remains largely unknown. Conversely, it is also unclear how peripheral myonuclei positioning is lost in the related muscle diseases. Here, we describe the microtubule-associated protein, MACF1, as an essential and evolutionary conserved regulator of myonuclei positioning and maintenance, in cultured mammalian myotubes, in Drosophila muscle, and in adult mammalian muscle using a conditional muscle-specific knockout mouse model. In vitro, we show that MACF1 controls microtubules dynamics and contributes to microtubule stabilization during myofiber's maturation. In addition, we demonstrate that MACF1 regulates the microtubules density specifically around myonuclei, and, as a consequence, governs myonuclei motion. Our in vivo studies show that MACF1 deficiency is associated with alteration of extra-synaptic myonuclei positioning and microtubules network organization, both preceding NMJ fragmentation. Accordingly, MACF1 deficiency results in reduced muscle excitability and disorganized triads, leaving voltage-activated sarcoplasmic reticulum Ca2+ release and maximal muscle force unchanged. Finally, adult MACF1-KO mice present an improved resistance to fatigue correlated with a strong increase in mitochondria biogenesis.
Subject(s)
Drosophila Proteins/metabolism , Drosophila melanogaster/metabolism , Microfilament Proteins/metabolism , Microtubules/metabolism , Mitochondria, Muscle/metabolism , Muscle Fibers, Skeletal/metabolism , Myoblasts, Skeletal/metabolism , Neuromuscular Junction/metabolism , Organelle Biogenesis , Animals , Cell Line , Drosophila Proteins/genetics , Drosophila melanogaster/genetics , Drosophila melanogaster/ultrastructure , Excitation Contraction Coupling , Mice, Inbred C57BL , Mice, Knockout , Microfilament Proteins/genetics , Microtubules/genetics , Microtubules/ultrastructure , Mitochondria, Muscle/genetics , Mitochondria, Muscle/ultrastructure , Muscle Fatigue , Muscle Fibers, Skeletal/ultrastructure , Muscle Strength , Myoblasts, Skeletal/ultrastructure , Neuromuscular Junction/genetics , Neuromuscular Junction/ultrastructure , Time FactorsABSTRACT
INTRODUCTION: The overnutrition is a constant on developing countries; Chile is not an exception because it has a marked tendency to overweight and obesity in schoolchildren. The muscular strength has been associated with cardiovascular and metabolic health status in scholars. Effective interventions using games are needed to improve the nutritional status and physical fitness in school children. OBJECTIVE: To assess the intervention effectiveness based on games played at school time to improve the nutritional status and physical fitness in schoolchildren. METHOD: 156 students aged between 7 to 15 years, attending to two public schools with full school day, to which a pilot program was applied. This pilot program was based on dynamic recreational games during 45 minutes from monday to friday for 3 months in the largest playtime of the school day. RESULTS: At the end of the intervention, we observed a significant modification on children nutritional status, which highlights an increase in the number of children that reached the normal nutritional status (p < 0.001). We also observed a significant number of obese children who reached overweight nutritional status (p < 0.001). We also observed a decrease of leg muscular strength at the end of the study. CONCLUSIONS: We found a positive effect of a program based on dynamic recreational games in the largest school playtime, improving nutritional status. However, we didn't observed modifications in the muscular strength.
INTRODUCCIÓN: La malnutrición por exceso es una constante en países en vías de desarrollo, Chile no es una excepción ya que existe una marcada tendencia hacia el sobrepeso y obesidad en la población escolar. La fuerza muscular ha sido asociada con un adecuado estado de salud cardiovascular y metabólica en la población escolar. Se necesitan intervenciones efectivas, que utilicen herramientas lúdicas y que permitan mejorar el estado nutricional y la capacidad física de los escolares. OBJETIVO: Valorar la efectividad de una intervención basada en juegos realizados dentro de la jornada escolar de los niños para mejorar el estado nutricional y la fuerza muscular. MÉTODO: 156 escolares de 7 a 15 años, pertenecientes a dos colegios municipalizados con jornada escolar completa, participaron de un programa piloto basado en juegos recreativos dinámico durante 45 minutos de lunes a viernes durante 3 meses, en el recreo más extenso de la jornada escolar. RESULTADOS: Al finalizar la intervención se observó una modificación estadísticamente significativa en el estado nutricional, donde destaca un aumento de niños que alcanza el estado nutricional normal. En aquellos que fueron clasificados previamente como obesos se logra modificar su estado nutricional hacia sobrepeso (p < 0,001). Se observó una disminución de la fuerza muscular del tren inferior al término del estudio (p < 0,001). CONCLUSIONES: Se demostró el impacto positivo de una intervención basada en juegos recreativos dinámicos durante los recreos escolares, con modificación positiva en el estado nutricional, pero sin mejoría de la fuerza muscular de los escolares.
Subject(s)
Exercise , Games, Recreational , Muscle Strength , Nutritional Status , Physical Fitness , Adolescent , Child , Female , Humans , Male , Obesity/therapy , Overweight/therapy , Pilot Projects , Schools , Treatment OutcomeABSTRACT
Introducción: La malnutrición por exceso es una constante en países en vías de desarrollo, Chile no es una excepción ya que existe una marcada tendencia hacia el sobrepeso y obesidad en la población escolar. La fuerza muscular ha sido asociada con un adecuado estado de salud cardiovascular y metabólica en la población escolar. Se necesitan intervenciones efectivas, que utilicen herramientas lúdicas y que permitan mejorar el estado nutricional y la capacidad física de los escolares. Objetivo: Valorar la efectividad de una intervención basada en juegos realizados dentro de la jornada escolar de los niños para mejorar el estado nutricional y la fuerza muscular. Método: 156 escolares de 7 a 15 años, pertenecientes a dos colegios municipalizados con jornada escolar completa, participaron de un programa piloto basado en juegos recreativos dinámico durante 45 minutos de lunes a viernes durante 3 meses, en el recreo más extenso de la jornada escolar. Resultados: Al finalizar la intervención se observó una modificación estadísticamente significativa en el estado nutricional, donde destaca un aumento de niños que alcanza el estado nutricional normal. En aquellos que fueron clasificados previamente como obesos se logra modificar su estado nutricional hacia sobrepeso (p < 0,001). Se observó una disminución de la fuerza muscular del tren inferior al término del estudio (p < 0,001). Conclusiones: Se demostró el impacto positivo de una intervención basada en juegos recreativos dinámicos durante los recreos escolares, con modificación positiva en el estado nutricional, pero sin mejoría de la fuerza muscular de los escolares (AU)
Introduction: The overnutrition is a constant on developing countries; Chile is not an exception because it has a marked tendency to overweight and obesity in schoolchildren. The muscular strength has been associated with cardiovascular and metabolic health status in scholars. Effective interventions using games are needed to improve the nutritional status and physical fitness in school children. Objective: To assess the intervention effectiveness based on games played at school time to improve the nutritional status and physical fitness in schoolchildren. Method: 156 students aged between 7 to 15 years, attending to two public schools with full school day, to which a pilot program was applied. This pilot program was based on dynamic recreational games during 45 minutes from monday to friday for 3 months in the largest playtime of the school day. Results: At the end of the intervention, we observed a significant modification on children nutritional status, which highlights an increase in the number of children that reached the normal nutritional status (p < 0.001). We also observed a significant number of obese children who reached overweight nutritional status (p < 0.001). We also observed a decrease of leg muscular strength at the end of the study. Conclusions: We found a positive effect of a program based on dynamic recreational games in the largest school playtime, improving nutritional status. However, we didnt observed modifications in the muscular strength (AU)
