Myostatin in combination with creatine phosphokinase or albumin may differentiate patients with cirrhosis and sarcopenia

Abstract

Background/Objectives:In patients with liver cirrhosis (LC), sarcopenia is correlated with frequent complications and increased mortality. Myostatin-a myokine-is a potential biomarker of skeletal mass and/or sarcopenia. The aim of this study was to examine the association between myostatin and muscle-mass and evaluate myostatin as a biomarker of sarcopenia in LC. Methods: Skeletal-muscle-index (SMI) and myosteatosis were evaluated by computed tomography scan. Muscle quantity and quality along with muscle strength and function were used to diagnose sarcopenia. Serum myostatin was measured by ELISA. Results:115 consecutive patients with LC [72.2% male, median age 59-years (IQR 52-67), MELD 12 (8-16), 28.7% with compensated LC] were included. Low SMI was diagnosed in 49.6% and sarcopenia in 34.8% (21.7% severe). Myostatin levels were lower in low (p<0.001) compared to normal SMI patients and were strongly correlated with SMI in MELD score≥15 (r=0.571, p<0.001). Myostatin was also lower in patients with sarcopenia compared to those without (p<0.001) and even lower in severe sarcopenia (p<0.001). In multivariate analysis, myostatin, age and albumin remained significant predictors of low SMI after adjustment for sex, MELD and creatine phosphokinase(CPK). Similarly, myostatin and age predicted sarcopenia after adjustment for sex, MELD, CPK and albumin. The ratios log10myostatin-to-CPK or albumin-to-myostatin were found to have acceptable diagnostic accuracy in ruling out sarcopenia in total patients. However, the best diagnostic performance was shown in MELD≥15 (AUROC 0.829 or 0.801, respectively). Conclusions:Myostatin is independently associated with both skeletal muscle mass and sarcopenia. Myostatin in combination with CPK or albumin are good surrogate markers in excluding sarcopenia.

Association between serum GDF-15, myostatin, and sarcopenia in cardiovascular surgery patients

“…However, myostatin secretion also increases when the skeletal muscle mass is high, and increased myostatin acts to control muscle mass [9] . A strong positive correlation between muscle mass index and myostatin was also found in advanced stages of liver cirrhosis, which was consistent with the fact that as liver disease worsens, the secretion of other muscle regulators such as testosterone [22] and insulin-like growth factor-1 (IGF-1) [23] decreases, and the role of myostatin as a muscle synthesis promoter becomes more important [21] . On the other hand, there are reports that myostatin and IGF-1 act as counter-regulatory molecules against muscle hypertrophy [10] , [24] .…”

“…In the present study, myostatin was low in patients with sarcopenia, and there are several reports on the mechanism of this phenomenon [9] , [10] , [21] . Myostatin suppresses muscle satellite cell differentiation, so when myostatin levels decrease after exercise, the decrease in myostatin promotes skeletal muscle anabolism.…”

“…In the present study, the sarcopenia index calculated from GDF-15 and myostatin was a strong regulator of sarcopenia in ROC curve analysis. Recently, some reports showed that myostatin was a biomarker to predict sarcopenia in patients [21] , [29] , [30] . In a previous study that performed ROC curve analysis for myostatin levels, the (log 10 myostatin) / creatine phosphokinase ratio and albumin / myostatin ratio were found to have acceptable diagnostic accuracy in ruling out sarcopenia in all patients with liver cirrhosis [21] .…”

Renal dysfunction independently predicts muscle mass loss in patients following liver transplantation

“…Model 1 included all variables + GFR, while Model 2 included all variables + creatinine levels. Covariates were chosen according to their potential effect on SMI reported in literature (14,15). P values < 0.05 were considered significant.…”

Generation of Heritable Prominent Double Muscle Buttock Rabbits via Novel Site Editing of Myostatin Gene Using CRISPR/Cas9 System

“…MSTN gene can code for TGF-beta (transforming growth factor-beta) superfamily ligand that can bind with different TGF-beta receptors and ultimately recruit or activate the SMAD family transcription factors, which regulate the gene expression ( 40 ). MSTN is a key regulator of muscle cell proliferation and differentiation throughout muscle development, and MSTN expression signals were detected from the early myogenic stage of embryonic sarcomere formation to the adult skeletal muscle development stage ( 14 , 41 , 42 ).…”