Malnutrition: muscle wasting, inflammation, RDW, and their relation with adverse outcomes.

OBJECTIVE: The objective of the study was to explore red cell distribution width (RDW) as a surrogate marker of inflammation, alone and in conjunction with muscle wasting to predict malnutrition-related adverse outcomes. METHODS: This was a single-center observational study including adult hospitalized patients. Demographic variables, malnutrition criteria, and RDW were captured within 24 hours of hospital admission. Correlation tests and regression models were performed between these variables (RDW and muscle wasting) and adverse outcomes (in-hospital mortality and unplanned transfer to critical care areas (CCA). RESULTS: Five hundred and forty-five patients were included in the final analysis. Muscle wasting showed an independent association with adverse outcomes in every regression model tested. RDW alone showed fair predictive performance for both outcomes' significance and the adjusted model with muscle wasting showed association only for unplanned transfer to CCA. CONCLUSION: RDW did not improve the prediction of adverse outcomes compared to muscle wasting assessed by physical examination and simple indexes for acute and chronic inflammation. Malnourished patients presented higher RDW values showing a possible metabolic profile (higher inflammation and lower muscle). It is still unknown whether nutrition support can influence RDW value over time as a response marker or if RDW can predict who may benefit the most from nutritional support.

OBJETIVO: Explorar el ancho de distribución eritrocitaria (ADE) como un marcador subrogado de inflamación, individualmente y en conjunto con el desgaste muscular, para predecir resultados adversos asociados a la desnutrición. MÉTODO: Estudio unicéntrico, observacional, incluyendo pacientes adultos hospitalizados. Se capturaron variables demográficas, criterios de desnutrición y el ADE en las primeras 24 horas de ingreso. Se realizaron pruebas de correlación y modelos de regresión entre dichas variables (ADE y desgaste) y resultados adversos (mortalidad hospitalaria y traslado no planeado a áreas críticas). RESULTADOS: Se incluyeron 545 pacientes. El desgaste muscular mostró asociación independiente con los resultados adversos en cada modelo. El ADE individualmente mostró un desempeño aceptable para la predicción de ambos resultados, y en modelos ajustados con desgaste muscular mostró asociación únicamente con traslado no planeado a áreas críticas. CONCLUSIONES: El ADE no mejoró la predicción de resultados adversos comparado con el desgaste muscular por exploración física e índices simples de inflamación. Los pacientes con desnutrición presentaron mayores valores de ADE, mostrando un posible perfil metabólico (mayor inflamación y menos músculo). Aún se desconoce si el soporte nutricional puede influenciar el ADE como un marcador de respuesta o si puede predecir una respuesta favorable al soporte nutricional.

Elevated serum Activin A in chronic obstructive pulmonary disease with skeletal muscle wasting.

OBJECTIVE: Muscle wasting contributes to the reduced quality of life and increased mortality in chronic obstructive pulmonary disease (COPD). Muscle atrophy in mice with cachexia was caused by Activin A binding to ActRIIB. The role of circulating Activin A leading to muscle atrophy in COPD remains elusive. METHODS: In the present study, we evaluated the relationship between serum levels of Activin A and skeletal muscle wasting in COPD patients. The expression levels of serum Activin A were measured in 78 stable COPD patients and in 60 healthy controls via ELISA, which was also used to determine the expression of circulating TNF-α levels. Total skeletal muscle mass (SMM) was calculated according to a validated formula by age and anthropometric measurements. The fat-free mass index (FFMI) was determined as the fat-free mass (FFM) corrected for body surface area. RESULTS: Compared to the healthy controls, COPD patients had upregulated Activin A expression. The elevated levels of Activin A were correlated with TNF-α expression, while total SMM and FFMI were significantly decreased in COPD patients. Furthermore, serum Activin A expression in COPD patients was negatively associated with both FFMI and BMI. CONCLUSION: The above results showed an association between increased circulating Activin A in COPD patients and the presence of muscle atrophy. Given our previous knowledge, we speculate that Activin A contributes to skeletal muscle wasting in COPD.

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.

Elevated serum Activin A in chronic obstructive pulmonary disease with skeletal muscle wasting

OBJECTIVE: Muscle wasting contributes to the reduced quality of life and increased mortality in chronic obstructive pulmonary disease (COPD). Muscle atrophy in mice with cachexia was caused by Activin A binding to ActRIIB. The role of circulating Activin A leading to muscle atrophy in COPD remains elusive. METHODS: In the present study, we evaluated the relationship between serum levels of Activin A and skeletal muscle wasting in COPD patients. The expression levels of serum Activin A were measured in 78 stable COPD patients and in 60 healthy controls via ELISA, which was also used to determine the expression of circulating TNF-α levels. Total skeletal muscle mass (SMM) was calculated according to a validated formula by age and anthropometric measurements. The fat-free mass index (FFMI) was determined as the fat-free mass (FFM) corrected for body surface area. RESULTS: Compared to the healthy controls, COPD patients had upregulated Activin A expression. The elevated levels of Activin A were correlated with TNF-α expression, while total SMM and FFMI were significantly decreased in COPD patients. Furthermore, serum Activin A expression in COPD patients was negatively associated with both FFMI and BMI. CONCLUSION: The above results showed an association between increased circulating Activin A in COPD patients and the presence of muscle atrophy. Given our previous knowledge, we speculate that Activin A contributes to skeletal muscle wasting in COPD.

A potential indicator of denervated muscle atrophy: the ratio of myostatin to follistatin in peripheral blood.

Myostatin is a secreted negative regulator of muscle mass, and follistatin antagonizes the function of several members of the TGF-b family, including myostatin. Previously, myostatin expression was found to be closely associated with atrophy of the gastrocnemius muscle, showing a linear correlation, after sciatic nerve injury. In this study, we investigated the possibility of myostatin being an indicator of denervated muscle atrophy. ELISA was used to detect the concentration of myostatin and follistatin in sera collected from individual rats at different times after sciatic nerve crush. A strong correlation was shown between the expression level of secreted myostatin in circulation and the wet weight ratio of the gastrocnemius muscle. The ratio of follistatin/myostatin could be used to monitor the progress of target muscle atrophy and recovery. Our study provides a potential serological test to detect denervated muscle atrophy for clinical purposes.

Leucine attenuates skeletal muscle wasting via inhibition of ubiquitin ligases.

The aim of this study was to assess the effect of leucine supplementation on elements of the ubiquitin-proteasome system (UPS) in rat skeletal muscle during immobilization. This effect was evaluated by submitting the animals to a leucine supplementation protocol during hindlimb immobilization, after which different parameters were determined, including: muscle mass; cross-sectional area (CSA); gene expression of E3 ligases/deubiquitinating enzymes; content of ubiquitinated proteins; and rate of protein synthesis. Our results show that leucine supplementation attenuates soleus muscle mass loss driven by immobilization. In addition, the marked decrease in the CSA in soleus muscle type I fibers, but not type II fibers, induced by immobilization was minimized by leucine feeding. Interestingly, leucine supplementation severely minimized the early transient increase in E3 ligase [muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1] gene expression observed during immobilization. The reduced peak of E3 ligase gene expression was paralleled by a decreased content of ubiquitinated proteins during leucine feeding. The protein synthesis rate decreased by immobilization and was not affected by leucine supplementation. Our results strongly suggest that leucine supplementation attenuates muscle wasting induced by immobilization via minimizing gene expression of E3 ligases, which consequently could downregulate UPS-driven protein degradation. It is notable that leucine supplementation does not restore decreased protein synthesis driven by immobilization.