Abstract

Myostatin (Mst) regulates skeletal muscle mass. Mst‐null (KO) mice have double muscle size, while Mst overexpression leads to skeletal muscle wasting. We aimed at identifying the role of Mst in adult‐onset atrophy, hypertrophy, physical performance and the involved molecular cascades. Fiber type composition of Mst overexpressing transgenic (Tg), Mst KO and WT male 1 year old mice (n=6 in each group) was assessed by immunohistochemistry, MHC isoforms by gel electrophoresis and gene expression levels by real time RT‐PCR from muscle tissues. Exercise tolerance was measured by incremental treadmill tests performed to exhaustion 3 times a week for 8 weeks. The initial speed was set to 8 m/min at no inclination. The speed and inclination were subsequently incremented by 4 m/min and 5% every 5 min. Exercise tolerance of KO animals was significantly lower than Tg animals (1.5±1.6 mJ/g vs. 7.3±4.1 mJ/g, P<0.05). In Tg animals the abdominal fat increased by 150% while the muscle mass decreased by 25%. Compared to wild type animals, the fast type fibers decreased by 22% in Tg animals while it increased by 25% in KO. The amount of MHC IIb protein was 2.2 fold higher in KO mice and MHC I was 1.8 fold higher in Tg animals. The Tg mice had a 37% increase in Mst mRNA expression and Akt2 expression was down‐regulated. We conclude that Mst plays a crucial role in regulating body composition, muscle structure and physical performance.

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