Experimental Model of HindLimb Suspension-Induced Skeletal Muscle Atrophy in Rodents.

Due to the difficulty of performing research protocols that reproduce human skeletal muscle disuse conditions, an experimental animal model of "hindlimb suspension" (or hindlimb unloading) was developed. This method was created in the 1970s and utilizes rats and mice to mimic space flight and bed rest in humans. It provides an alternative to investigate mechanisms associated with skeletal muscle mass loss and interventions designed to attenuate atrophy induced by hindlimb unloading. The mentioned protocol also allows investigating quality of bones and changes in several physiological parameters such as blood pressure, heart rate, plasma or tissue lipid composition, and glycemia.

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.

Balanced Diet-Fed Fat-1 Transgenic Mice Exhibit Lower Hindlimb Suspension-Induced Soleus Muscle Atrophy.

The consequences of two-week hindlimb suspension (HS) on skeletal muscle atrophy were investigated in balanced diet-fed Fat-1 transgenic and C57BL/6 wild-type mice. Body composition and gastrocnemius fatty acid composition were measured. Skeletal muscle force, cross-sectional area (CSA), and signaling pathways associated with protein synthesis (protein kinase B, Akt; ribosomal protein S6, S6, eukaryotic translation initiation factor 4E-binding protein 1, 4EBP1; glycogen synthase kinase3-beta, GSK3-beta; and extracellular-signal-regulated kinases 1/2, ERK 1/2) and protein degradation (atrophy gene-1/muscle atrophy F-box, atrogin-1/MAFbx and muscle RING finger 1, MuRF1) were evaluated in the soleus muscle. HS decreased soleus muscle wet and dry weights (by 43% and 26%, respectively), muscle isotonic and tetanic force (by 29% and 18%, respectively), CSA of the soleus muscle (by 36%), and soleus muscle fibers (by 45%). Fat-1 transgenic mice had a decrease in the ω-6/ω-3 polyunsaturated fatty acids (PUFAs) ratio as compared with C57BL/6 wild-type mice (56%, p < 0.001). Fat-1 mice had lower soleus muscle dry mass loss (by 10%) and preserved absolute isotonic force (by 17%) and CSA of the soleus muscle (by 28%) after HS as compared with C57BL/6 wild-type mice. p-GSK3B/GSK3B ratio was increased (by 70%) and MuRF-1 content decreased (by 50%) in the soleus muscle of Fat-1 mice after HS. Balanced diet-fed Fat-1 mice are able to preserve in part the soleus muscle mass, absolute isotonic force and CSA of the soleus muscle in a disuse condition.

Metabolic and morphometric alterations inherent to neuromuscular electric stimulation in the antagonist muscle submitted to ankle joint immobilization

The aim of this work was to investigate the effect of the neuromuscular electrical stimulation (ES) on the metabolic and morfometric profile of the tibialis anterior muscle, antagonist to the soleus muscle which was stimulate, under the joint immobilization condition of the ankle for 7 and 15 days. The immobilization promoted the reduction in the muscle mass (I7: 17.36 percent, I15: 20.83 percent), in the glycogen content (I7: 48 percent, I15: 48 percent), in the muscle fibers areas (I7: 27 percent, I15: 40 percent) and increase in intramuscular connective tissue density (I7: 122 percent, I15: 206 percent). The EE didn't promote significant alterations in the mass of the immobilized groups, however, promoted increase in the glycogen (IEE7: 31.25 percent; IEE15: 56.25 percent), reduction in the muscle fibers areas (IEE7: 14 percent, IEE15: 24.69 percent) and reduction in the connective tissue density (IEE7: 25.63 percent, IEE15: 49.09 percent) when compared with the respective immobilized groups.

O objetivo desse trabalho foi investigar o efeito da estimulação elétrica neuromuscular (EE) sobre o perfil metabólico e morfométrico do músculo tibial anterior, antagonista ao músculo sóleo, o qual foi estimulado, sob a condição de imobilização articular de tornozelo durante 7 e 15 dias. A imobilização promoveu redução na massa muscular (I7: 17,36 por cento, I15: 20,83 por cento), no conteúdo de glicogênio (I7: 48 por cento, I15: 48 por cento), na área das fibras musculares (I7: 27 por cento, I15: 40 por cento) e aumento na densidade do tecido conjuntivo intramuscular (I7: 122 por cento, I15: 206 por cento). A EE não promoveu alterações significativas na massa muscular dos grupos imobilizados, porém, promoveu aumento no glicogênio (IEE7: 31,25 por cento; IEE15: 56,25 por cento), redução na área das fibras musculares (IEE7: 14 por cento, IEE15: 24,69 por cento) e redução na densidade do tecido conjuntivo de (IEE7: 25,63 por cento, IEE15: 49,09 por cento) quando comparado aos respectivos grupos imobilizados.

Metformin protects the skeletal muscle glycogen stores against alterations inherent to functional limitation

The aim of this study was to evaluate the glycogen content (GC) of the rat hind limb muscles submitted to joint immobilization, either associated with metformin treatment (M, 1,4mg.ml-1) or not. In the metformin group, there was a significant increase in the GC (soleus - S 65 percent , white gastrocnemius - WG 30.5 percent, red gastrocnemius- RG31.7 percent, extensor digitorum longus - EDL 44 percent, tibialis anterior- TA 77.4 percent). The immobilization significantly reduced the GC (S 31.6 percent, WG 56.6 percent, RG 39.1 percent, ELD 41.7 percent, TA 45.2 percent) and weight (S 34.2 percent and ELD 27 percent), whereas in the group immobilized with the metformin, there was an increase in the GC of all the muscles (S 177 percent, WG 290 percent, RG 172 percent,ELD 47 percent, TA 217 percent), in addition to minimizing the weight loss of S (29.6 percent) and ELD (27.8 percent).

O objetivo deste estudo foi avaliar o conteúdo de glicogênio (GLI) da musculatura da pata posterior de ratos submetidos à imobilização articular, associado ou não ao tratamento com metformina (MET, 1,4 mg.ml -1) no período de sete dias. No grupo metformina, houve elevação significativa nas RG (65 por cento no sóleo - S, 30.5 por cento no gastrocnêmio branco - GB, 31.7 por cento no gastrocnêmio vermelho - GV , 44 por cento no extensor longo dos dedos - EDL e de 77.4 por cento no tibial anterior - TA ). A imobilização reduziu significativamente as RG (S 31,6 por cento, GB 56,6 por cento, GV 39,1 por cento, ELD 41,7 por cento, TA 45,2 por cento) e peso (S 34,2 por cento e ELD 27 por cento), já no grupo imobilizado com metformina houve o aumento das RG de todos os músculos (S 177 por cento, GB 290 por cento, GV 172 por cento,EDL 47 por cento, TA 217 por cento), além de minimizar a perda de peso do S (29,6 por cento) e ELD (27,8 por cento).