Sarcopenia associated with portosystemic shunting is reversed by follistatin

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• 作者：Srinivasan Dasarathy¹ ; ² ; ^{dasaras@ccf.org} ; Arthur J. McCullough¹ ; ² ; Sean Muc¹ ; ² ; Alan Schneyer³ ; Carole D. Bennett¹ ; ² ; Milan Dodig¹ ; ² ; Satish C. Kalhan¹ ; ²
• 关键词：Skeletal muscle loss ; Liver disease ; Portacaval anastamosis ; Myostatin
• 刊名：Journal of Hepatology
• 出版年：2011
• 出版时间：May 2011
• 年：2011
• 卷：54
• 期：5
• 页码：915-921
• 全文大小：1245 K

文摘

Background & Aims

The distinct role of portosystemic shunting (PSS) in the pathogenesis of sarcopenia (skeletal muscle loss) that occurs commonly in cirrhosis is unclear. We have previously shown increased expression of myostatin (inhibitor of skeletal muscle mass) in the portacaval anastamosis (PCA) rat model of sarcopenia of PSS. The present study was performed to examine the mechanisms of sarcopenia following PCA.

Methods

In PCA and sham operated pair fed control rats, the phenylalanine flooding dose method was used to quantify the fractional and absolute protein synthesis rates in the skeletal muscle over time and in response to follistatin, a myostatin antagonist. The expression of myostatin and markers of satellite cell (myocyte precursors) proliferation and differentiation were quantified by real-time PCR and Western blot analyses.

Results

The absolute synthesis rate (ASR) was lower at 2, 4, and 6 weeks (p <0.05) and the fractional synthesis rate (FSR) of skeletal muscle protein was significantly lower (p <0.05) at week 2 in the PCA rats compared to control rats. Expression of myostatin was elevated while markers of satellite cell proliferation and differentiation were lower at 4 and 6 weeks after PCA. Follistatin increased skeletal muscle mass, muscle FSR and ASR, decreased expression of myostatin protein, and increased expression of markers of satellite cell function.

Conclusions

Sarcopenia associated with PSS is caused by impaired protein synthesis and reduced satellite cell function due to increased myostatin expression. Confirming these alterations in human patients with cirrhosis will provide novel therapeutic targets for sarcopenia of liver disease.