Simulated weightlessness led to the transformation of glycolipid metabolism in the livers of mice / La antigravedad simulada provocó la transformación del metabolismo de los glicolípidos en el hígado de ratones / Antigravidade simulada levou à transformação do metabolismo de glicolipídios no fígado de camundongos

ABSTRACT Objectives: The effects of weightlessness on the liver were studied using a tail suspension (TS) male mouse model. Methods: The effects of 0-, 2- and 4-week TS (CON, TS2 and TS4 groups) on glycogen and lipid content, as well as on the molecular processes of the synthesis and degradation pathways, were examined. Results: (1) The number of glycogenosomes under ultrastructure and the glycogen content were considerably larger in the TS4 group than in the other two groups. (2) In the TS4 group, glycogen synthase activity remained constant while glycogen phosphorylase activity dropped, indicating that glycogen breakdown was reduced. (3) The livers of the TS2 group had the highest lipid and triglyceride content, indicating lipid buildup in the liver at this time. (4) In the TS2 group, the activities of the fatty acid synthesis-related factors acetyl-CoA carboxylase and fatty acid synthase increased, while hepatic lipase decreased, indicating that lipid synthesis increased, while decomposition decreased. (5) In the TS2 group, the protein expression of glucose transporters 1 and 2 increased. Conclusions: From TS2 weeks to TS4 weeks, the main energy consumption mode in the livers of mice transitioned from glucose metabolism to lipid metabolism as glucose use decreased. Level of evidence II; Comparative prospective study.

RESUMEN Objetivos: Se estudiaron los efectos de la antigravedad en el hígado utilizando un modelo de ratón macho en prueba de suspensión de la cola (TS, tail suspension). Métodos: Se examinaron los efectos de la TS a las 0, 2 y 4 semanas (grupos CON, TS2 y TS4) sobre el contenido de glucógeno y lípidos, así como sobre los procesos moleculares de las vías de síntesis y degradación. Resultados: (1) El número de glucogenosomas ultraestructurales y el contenido de glucógeno fueron expresivamente más altos en el grupo TS4 que en los otros dos grupos. (2) En el grupo TS4, la actividad de la glucógeno sintasa se mantuvo constante, mientras que la actividad de la glucógeno fosforilasa disminuyó, lo que indica que la degradación del glucógeno se redujo. (3) Los hígados del grupo TS2 presentaron el mayor contenido de lípidos y triglicéridos, lo que indica la acumulación de lípidos en el hígado en ese momento. (4) En el grupo TS2, la actividad de los factores relacionados con la síntesis de ácidos grasos acetil-CoA carboxilasa y ácido graso sintasa aumentó, mientras que la lipasa hepática disminuyó, indicando que la síntesis de lípidos aumentó mientras que la descomposición disminuyó. (5) En el grupo TS2, la expresión proteica de los transportadores de glucosa 1 y 2 aumentó. Conclusiones: Desde la semana TS2 hasta la semana TS4, el principal modo de consumo de energía en el hígado de los ratones pasó del metabolismo de la glucosa al metabolismo de los lípidos a medida que disminuía el uso de la glucosa. Nivel de Evidencia II, Estudio retrospectivo comparativo.

RESUMO Objetivos: Os efeitos da antigravidade no fígado foram estudados usando um modelo de camundongo macho com a suspensão pela cauda (TS, tail suspension). Métodos: Foram examinados os efeitos da TS em 0, 2 e 4 semanas (grupos CON, TS2 e TS4) sobre o conteúdo de glicogênio e lipídios, bem como nos processos moleculares das vias de síntese e degradação. Resultados: (1) O número de glicogenossomos ultraestruturais e o teor de glicogênio foram expressivamente maiores no grupo TS4 do que nos outros dois grupos. (2) No grupo TS4, a atividade de glicogênio sintase permaneceu constante, enquanto a atividade de glicogênio fosforilase caiu, indicando que a degradação do glicogênio foi reduzida. (3) Os fígados do grupo TS2 tiveram o maior teor lipídico e de triglicérides, indicando acúmulo de lipídios no fígado no momento. (4) No grupo TS2, a atividade dos fatores relacionados com a síntese de ácidos graxos acetil-CoA carboxilase e ácido graxo sintase aumentaram, enquanto a lipase hepática diminuiu, indicando que a síntese de lipídios aumentou, enquanto a decomposição diminuiu. (5) No grupo TS2, a expressão proteica dos transportadores de glicose 1 e 2 aumentou. Conclusões: De TS2 semanas para TS4 semanas, o principal modo de consumo de energia no fígado de camundongos passou do metabolismo da glicose para o metabolismo lipídico, à medida que o uso de glicose diminuiu. Nível de evidência II, Estudo retrospectivo comparativo.

Core training under suspension exercise therapy on treatment of low back pain / Treinamento de core com terapia de exercícios de suspensão para a dor lombar / Entrenamiento del core con terapia de ejercicios en suspensión para el dolor lumbar

ABSTRACT Introduction: The main clinical feature of chronic nonspecific low back pain (CNLBP) is lower back pain, and suspension sports therapy has a specific effect in this case. Objective: To investigate the changes of flexion-relaxation phenomenon in patients with lower back pain after core control training of suspension exercise therapy (SET). Methods: 84 subjects who met the inclusion and exclusion criteria of chronic low back pain in this experiment were randomly divided into an experimental group and a control group. The experimental group was treated with suspension training. The control group only received acupuncture. We then determined the muscle fascia tension and core stability of the lower lumbar region. Results: The visual analog scale (VAS) and Oswestry dysfunction index (ODI) evaluations of the two groups of patients were different. Conclusion: Suspended core stabilization training has a significant long-term effect in reducing lower back pain and improving waist function in patients with chronic nonspecific low back pain. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: A característica clínica principal da dor lombar crônica não especifica (CNLBP) é dor na região lombar. A terapia esportiva por suspensão tem um efeito específico neste caso. Objetivo: Investigar as mudanças do fenômeno flexão- relaxamento em pacientes com dor lombar após treinamento de controle core com terapia de exercícios de suspensão (SET). Métodos: 84 indivíduos que preencheram os critérios de inclusão e exclusão para dor lombar crônica neste experimento foram aleatoriamente divididos em um grupo experimental e um grupo de controle. O grupo experimental foi tratado com treinamento de suspensão. O grupo de controle recebeu apenas acupuntura. Determinamos então a tensão da fáscia muscular e a estabilidade core da região lombar. Resultados: Avaliações da escala visual analógica (EVA) e do índice de incapacidade Owestry (ODI) dos dois grupos de pacientes tiveram resultados diferentes. Conclusão: O treinamento de estabilização do core por suspensão tem efeito de longo prazo considerável na redução de dor lombar e a recuperação da função da cintura em pacientes com dor lombar não especifica crônica. Nível de evidência II; Estudos terapêuticos - investigação de resultados de tratamento.

Resumen Introducción: La característica clínica principal del dolor lumbar crónico inespecífico (CNLBP) es dolor en la región lumbar. La terapia deportiva en suspensión tiene un efecto específico en este caso. Objetivo: Investigar los cambios del fenómeno flexión-relajamiento en pacientes con dolor lumbar tras el entrenamiento de control de core con terapia de ejercicios en suspensión (SET). Métodos: Se dividió aleatoriamente los 84 individuos que rellenaron los criterios de inclusión y exclusión para dolor lumbar crónico en este experimento en un grupo experimental y un grupo de control. El grupo experimental fue tratado con entrenamiento en suspensión. El grupo de control recibió apenas acupuntura. Determinamos, entonces, la tensión de la fascia muscular y la estabilidad core de la región lumbar. Resultados: Evaluaciones de escala visual analógica (EVA) y del índice de discapacidad Owestry (ODI) de los dos grupos tuvieron resultados diferentes. Conclusión: El entrenamiento de estabilización del core por suspensión tiene efecto de largo plazo considerable en la reducción de dolor lumbar y la recuperación de la función de la cintura en pacientes con dolor lumbar inespecífico crónico. Nivel de evidencia II; Estudios terapéuticos - investigación de resultados de tratamiento.

Short-term creatine supplementation changes protein metabolism signaling in hindlimb suspension

The effect of a short-term creatine supplementation on hindlimb suspension (HS)-induced muscle atrophy was investigated. Creatine monohydrate (5 g/kg b.w. per day) or placebo, divided in 2 daily doses, was given by oral gavage for 5 days. Rats were maintained in HS with dietary supplementation concomitantly for 5 days. Body weight, soleus and EDL muscle masses, and cross-sectional areas (CSA) of the muscle fibers were measured. Signaling pathways associated with skeletal muscle mass regulation (FST, MSTN, FAK, IGF-1, MGF, Akt, mTOR, atrogin-1, and MuRF1 expressions, and Akt, S6, GSK3B, and 4EBP1 proteins) were evaluated in the muscles. Soleus muscle exhibited more atrophy than the EDL muscle due to HS. Creatine supplementation attenuated the decrease of wet weight and increased p-4EBP1 protein in the EDL muscle of HS rats. Also, creatine increased mTOR and atrogin-1 expressions in the same muscle and condition. In the absence of HS, creatine supplementation increased FAK and decreased MGF expressions in the EDL muscle. Creatine attenuated the increase in FST expression due to HS in the soleus muscle. MuRF1 expression increased in the soleus muscle due to creatine supplementation in HS animals whereas atrogin-1 expression increased still further in this group compared with untreated HS rats. In conclusion, short-term creatine supplementation changed protein metabolism signaling in soleus and EDL muscles. However, creatine supplementation only slightly attenuated the mass loss of both muscles and did not prevent the CSA reduction and muscle strength decrease induced by HS for 5 days.

Sarcomere structure: the importance of desmin protein in muscle atrophy / Estructura de sarcómera: la importancia de proteína desmina en atrofia muscular

Knowing the ultrastructure of skeletal muscle is critical to understand how it works under normal situation and the disorders caused by extreme or pathological conditions. Sarcomere is the basic structural unit of striated muscle tissue. An important element of sarcomere architecture are the intermediate filaments, including the desmin protein. Desmin protein contributes to maintenance of cell integrity, efficient transmission of force and mechanochemical signaling within the myocyte. Because of this, desmin protein has constantly been a focus of research that investigates its alterations associated to damage and muscle atrophy under different conditions. The purpose of the following literature review is to describe the basic concepts of muscle ultrastructure, emphasizing the desmin protein role under conditions of muscle disuse atrophy and aging.

Conocer la ultraestructura del músculo esquelético es crítico para entender cómo trabaja bajo situaciones normales y en desórdenes causados por condiciones extremas o patológicas. La sarcómera es la unidad de estructura básica del tejido muscular estriado. Elementos importantes en la arquitectura de la sarcómera son los filamentos intermedios, incluyendo la proteína desmina. La proteína desmina contribuye en mantener la integridad celular, la transmisión eficiente de fuerza y la señalización mecanoquímica dentro del miocito. Debido a lo anterior, la proteína desmina ha sido constante foco de investigación en trabajos que estudian sus alteraciones asociadas a daño y atrofia muscular bajo diferentes condiciones. El propósito de la siguiente revisión de la literatura es describir los conceptos básicos de la ultraestructura muscular, enfatizando en el rol de la proteína desmina bajo condiciones de atrofia muscular por desuso y envejecimiento.

Effect of Long-Term Antiorthostatic Suspension in a Murine Model of Acute Lung Injury

OBJECTIVES: Antiorthostatic suspension (AOS) is ground-based model of simulated microgravity. There is still no study about the effect of long-term microgravity on the clinical course of acute lung injury. We evaluated the effect of simulated microgravity using AOS in a murine model of acute lung injury by lipopolysaccharide (LPS). METHODS: Thirty BALB/c mice were used. During 4 weeks, mice were equally allocated to control (free movement), restraint (tail suspended, but hindlimbs not unloaded), and AOS group (hindlimb unloaded). After then, mice got intranasal challenge with LPS (20 mg/kg, 50 μL). We measured: weight gain before and after AOS, the number of inflammatory cells and titers of cytokines (interleukin [IL]-1β, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) in bronchoalveolar lavage (BAL) fluid, titer of myeloperoxidase (MPO) in serum and lung homogenate, and histopathologic examination of lung tissue. RESULTS: AOS group had significant weight loss compared to control and restraint group (P<0.001). AOS group also showed significantly decreased lymphocytes (P=0.023) compared to control group. In AOS group, titer for IL-1β in BAL fluid was significantly lower than restraint group (P=0.049). Titer for serum MPO was significantly decreased in AOS group compared to restraint group (P=0.004). However, there was no significant difference of MPO titers in lung tissue between groups. Histopathologic examination of lung tissue revealed no significant difference in the degree of pulmonary infiltration between restraint and AOS group. CONCLUSION: In spite of modest anti-inflammatory effect, prolonged AOS caused no significant change in LPS-induced pulmonary inflammation.

Expression of hypoxia inducing factor-1α in rats' ovary under tail-suspension weightlessness / 解放军医学杂志

Objective To investigate the expression feature of hypoxia inducing factor-1α (HIF-1α) in rats' ovary under simulated weightlessness. Methods Sixty adult female Wistar rats, weight 200±20g, were randomly divided into 10 groups (6 each): a control group without simulating weightlessness, and experimental groups underwent tail suspension for 0.25, 0.5, 1, 2, 3, 5, 7, 14 and 21-day, respectively. The HIF-1α expression in rats' ovaries was assessed by immunohistochemical staining and RT-PCR assay. Results Positively stained HIF-1α was observed as brown particle in follicular oocytes, granulosa cells and thecal cells of rat ovaries in both experimental and control groups. The positively stained HIF-1α granules mainly located in the cytoplasm of ovarian cells in control group, while in tail-suspension 0.25-day and 0.5-day groups, the granules transferred from cytoplasm to nucleus of follicular oocytes, granulosa cells and thecal cells. The expression level in tail-suspension 1-day group was similar to that in control group, and the staining of nuclei disappeared. The expression level of HIF-1α mRNA was significantly higher in tail-suspension 0.25-day and 0.5-day groups than that in control group (P<0.05). One day after tail-suspension, the expression levels of both HIF-1α protein and HIF-1α mRNA gradually recovered to that of control group. Conclusion The simulated weightlessness by tail-suspension, serving as a kind of stress, may increase the expression of both HIF-1α protein and HIF-1α mRNA in rat ovary during the early period, implying that a close correlation between the HIF-1α expression in rats' ovary and the weightlessness stress tolerance.

Expression of hypoxia inducing factor-1α in rats' ovary under tail-suspension weightlessness / 解放军医学杂志

Objective To investigate the expression feature of hypoxia inducing factor-1α (HIF-1α) in rats' ovary under simulated weightlessness. Methods Sixty adult female Wistar rats, weight 200±20g, were randomly divided into 10 groups (6 each): a control group without simulating weightlessness, and experimental groups underwent tail suspension for 0.25, 0.5, 1, 2, 3, 5, 7, 14 and 21-day, respectively. The HIF-1α expression in rats' ovaries was assessed by immunohistochemical staining and RT-PCR assay. Results Positively stained HIF-1α was observed as brown particle in follicular oocytes, granulosa cells and thecal cells of rat ovaries in both experimental and control groups. The positively stained HIF-1α granules mainly located in the cytoplasm of ovarian cells in control group, while in tail-suspension 0.25-day and 0.5-day groups, the granules transferred from cytoplasm to nucleus of follicular oocytes, granulosa cells and thecal cells. The expression level in tail-suspension 1-day group was similar to that in control group, and the staining of nuclei disappeared. The expression level of HIF-1α mRNA was significantly higher in tail-suspension 0.25-day and 0.5-day groups than that in control group (P<0.05). One day after tail-suspension, the expression levels of both HIF-1α protein and HIF-1α mRNA gradually recovered to that of control group. Conclusion The simulated weightlessness by tail-suspension, serving as a kind of stress, may increase the expression of both HIF-1α protein and HIF-1α mRNA in rat ovary during the early period, implying that a close correlation between the HIF-1α expression in rats' ovary and the weightlessness stress tolerance.

Effect of electro-acupuncture on skeletal muscle atrophy in mice / 全日本鍼灸学会雑誌

[Objective]Skeletal Muscle atrophy is induced in response to unloading by Hindlimb Suspension (HS). Numerous studies have been performed to prevent Skeletal Muscle atrophy. However, the molecular mechanisms underlying Electro-acupuncture (EA) on skeletal muscle have not been identified, and the effect of EA to prevent skeletal muscle atrophy is unknown. Therefore, we aimed to determine the effect of EA and Chishin (where the needles are kept in muscle for thirty minutes) on skeletal muscle atrophy in an animal experiment.<BR>[Methods]Twenty mice (8 week, C57BL6) were randomly grouped into 4 groups;Normal group (N group), Hindlimb Suspension Group (HS group), HS +Chishin group (Chishin group), and HS +EA 1Hz group (1Hz group) (n = 5/group, respectively). Acupuncture interventions were conducted on the gastrocnemius of the Chishin and 1Hz groups. We measured the muscle mass, the cross sectional area, the percentage of Antrogin-1 and MuRF1 (Atrophy related E3ubiquitin ligases) expressions of the soleus 0f each mouse at 2 weeks after acupuncture interventions.<BR>[Result]The weight and Cross sectional area of the soleus of the 1Hz group were significantly greater than the HS group (P<0.01, P<0.01, respectively). On the contrary, the percentage of Atrogin-1 and MuRF1 expressions of the 1Hz group was significantly less than the HS groups (P<0.01, P<0.05, respectively).<BR>[Conclusion]These results suggest that EA and Chishin may influence the activity of Atrogin-1 &MuRF1 expression.

Electroacupuncture accelerates recovery of muscle atrophy induced by hindlimb suspension in mouse skeletal muscle / 全日本鍼灸学会雑誌

[Objective]The influence of electroacupuncture (EA) stimulation on physical inactivity is not clear. This study aimed to investigate the effects of EA on the recovery of mouse soleus muscle atrophy induced by hindlimb suspension (HS).<BR>[Methods]We used 8-week-old male ICR mice (n = 20). The mice were divided into 4 groups:the No treatment group (NT, n = 5), HS group (HS, n = 5), Control group (CT, n = 5), and Reloading-with-EA-stimulation group (EA, n = 5). HS mice were suspended for up to 14 days. CT and EA mice were reloaded for an additional 14 days after the HS for 14 days. The HS method used a modified version of an apparatus used in a previous study. EA mice received EA every other day immediately after reloading and were stimulated in the triceps surae muscle at 10 Hz for 30 min with a stainless steel needle. The weight, muscle fiber area size and number of macrophages in the soleus muscle were analyzed.<BR>[Results]The number of skeletal muscle macrophages was increased significantly in EA mice compared with that in CT mice (P < 0.01). The soleus muscle weight and muscle fiber cross-sectional area were decreased in HS mice compared with NT mice (P < 0.01). However, the muscle weight of EA and CT mice increased significantly compared with that of HS mice (P < 0.01). In addition, the muscle weight of EA mice was significantly higher than that of CT mice (P < 0.01), without a significant difference in muscle fiber cross-sectional area between CT and EA mice. <BR>[Conclusion]These results indicate that EA was effective in facilitating the recovery of skeletal muscle atrophy in mice. In addition, resolution of the skeletal muscle atrophy suggested the satellite cell activation by macrophages, because macrophages invaded the skeletal muscle after EA stimulation.

EFFECTS OF COMBINATION OF HEAT STRESS AND ASTAXANTHIN SUPPLEMENTATION ON DISUSE MUSCLE ATROPHY / 体力科学

The purpose of this study was to examine the effects of combination of a heat stress and astaxanthin supplementation, known as a potent anti-oxidative nutrient, on muscle protein degradation and disuse muscle atrophy. Fifty-two male Wistar rats (261.7±1.17 g) were divided into five groups: control (Cont, n=10), suspension (Sus, n=11), heat stress and suspension (Heat, n=10), astaxanthin and suspension (Ax, n=10), and heat stress, astaxanthin and suspension (H+A, n=11). There were no significant differences in Cu,Zn-SOD, cathepsin L and caspase-3 levels among the Heat, Ax and H+A groups in the soleus and plantaris muscles. Although levels of calpain 2 and ubiquitinated protein in the myofibrillar fraction in the soleus muscle were not significantly different among the Heat, Ax and H+A groups, levels in the H+A group were significantly (p<0.05) lower than Sus. Concerning atrophied plantaris muscles, the H+A group significantly (p<0.05) suppressed the expression of calpain 1 in the myofibrillar fraction, but there were no marked changes of proteolytic indexes. These data indicate that the combination of the heat stress and astaxanthin supplementation could be effective in inhibiting muscle protein degradation in disuse atrophy of the soleus.

Biomechanics and structural adaptations of the rat femur after hindlimb suspension and treadmill running

We microscopically and mechanically evaluated the femurs of rats subjected to hindlimb unloading (tail suspension) followed by treadmill training. Female Wistar rats were randomly divided into five groups containing 12-14 rats: control I (118 days old), control II (139 days old), suspended (tail suspension for 28 days), suspended-released (released for 21 days after 28 days of suspension), and suspended-trained (trained for 21 days after 28 days of suspension). We measured bone resistance by bending-compression mechanical tests of the entire proximal half of the femur and three-point bending tests of diaphyseal cortical bone. We determined bone microstructure by tetracycline labeling of trabecular and cortical bone. We found that tail suspension weakened bone (ultimate load = 86.3 ± 13.5 N, tenacity modulus = 0.027 ± 0.011 MPa·m vs ultimate load = 101.5 ± 10.5 N, tenacity modulus = 0.019 ± 0.006 MPa·m in control I animals). The tenacity modulus for suspended and released animals was 0.023 ± 0.010 MPa·m vs 0.046 ± 0.018 MPa·m for trained animals and 0.035 ± 0.010 MPa·m for control animals. These data indicate that normal activity and training resulted in recovered bone resistance, but suspended-released rats presented femoral head flattening and earlier closure of the growth plate. Microscopically, we found that suspension inhibited new bone subperiosteal and endosteal formation. The bone disuse atrophy secondary to hypoactivity in rats can be reversed by an early regime of exercising, which is more advantageous than ordinary cage activities alone.

Mechanics and Fatigability of the Rat Soleus Muscle During Early Reloading

In order to elucidate muscle functional changes by acute reloading, contractile and fatigue properties of the rat soleus muscle were investigated at three weeks of hindlimb suspension and the following 1 hr, 5 hr, 1 d, and 2 weeks of reloading. Compared to age-matched controls, three weeks of unloading caused significant changes in myofibrillar alignments, muscle mass relative to body mass (-43%), normalized tension (-35%), shortening velocity (+143%), and response times. Further significant changes were not observed during early reloading, because the transitional reverse process was gradual rather than abrupt. Although most of the muscle properties returned to the control level after two weeks of reloading, full recovery of the tissue would require more than the two-week period. Delayed recovery due to factors such as myofibrillar arrangement and fatigue resistance was apparent, which should be considered for rehabilitation after a long-term spaceflight or bed-rest.

Time Course of Rat Soleus Muscle Fiber Composition and Motoneurons During Three Weeks Hindlimb Suspension / 体力科学

We examined the time course of soleus muscle fiber type composition. Soma area and succinate dehydrogenase (SDH) activity of soleus motoneurons during three weeks of hindlimb suspension (HS) in rats. Adult female Wistar rats (n=34, 252-288g BW) were divided into four groups: control (n=8), hindlimb suspended for one week (HS 1 wk, n=8), two weeks (HS 2 wk, n=9), and three weeks (HS 3 wk, n=9) . Soleus muscle fiber composition was calculated from transverse sections stained for myosin ATPase (preincubation pH 10.3, 4.3) . The fiber type composition did not change in the HS 1 wk, but in the HS 2 wk and HS 3 wk, the proportion of type I fibers decreased and that of type IIc and ha fibers increased. Using a fluorescent neuronal tracer nuclear yellow, motoneurons innervating the soleus muscle were identified, and the soma area and SDH activity were measured. The soma area did not change for up to two weeks of HS, but decreased in the HS 3 wk. Compared with control, SDH activity of soleus motoneurons decreased in the HS 1 wk. However, in the HS 2 wk, the activity increased to the level of control. In the HS 3 wk, the activity tended to increase further. Generally, muscle fibers and their motoneurons have unitary characteristics. However, these results suggest that change in soleus muscle fiber composition are not accompanied by changes in soma area and SDH activity in soleus motoneurons during three weeks of HS.