Open AccessThe anabolic catabolic transforming agent (ACTA) espindolol increases muscle mass and decreases fat mass in old rats
Author(s) -
Pötsch Mareike S.,
Tschirner Anika,
Palus Sandra,
von Haehling Stephan,
Doehner Wolfram,
Beadle John,
Coats Andrew J. S.,
Anker Stefan D.,
Springer Jochen
Publication year - 2014
Publication title -
journal of cachexia, sarcopenia and muscle
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.803
H-Index - 66
eISSN - 2190-6009
pISSN - 2190-5991
DOI - 10.1007/s13539-013-0125-7
Subject(s) - anabolism , medicine , sarcopenia , endocrinology , myostatin , lean body mass , placebo , protein kinase b , muscle atrophy , catabolism , skeletal muscle , weight loss , obesity , chemistry , phosphorylation , body weight , biochemistry , metabolism , pathology , alternative medicine
Background Sarcopenia, the age‐related, progressive loss of skeletal muscle mass, strength, and function, is a considerable socioeconomic burden by increasing risks of falls, fractures, and frailty. Moreover, sarcopenic patients are often obese and therapeutic options are very limited. Methods Here, we assessed the efficacy of espindolol on muscle mass in 19‐month‐old male Wistar Han rats (weight, 555 ± 18 g), including safety issues. Rats were randomized to treatment with 3 mg/kg/day espindolol ( n = 8) or placebo ( n = 14) for 31 days. Results Placebo‐treated rats progressively lost body weight (−15.5 ± 7.2 g), lean mass (−1.5 ± 4.2 g), and fat mass (−15.6 ± 2.7 g), while espindolol treatment increased body weight (+8.0 ± 6.1 g, p < 0.05), particularly lean mass (+43.4 ± 3.5 g, p < 0.001), and reduced fat mass further (−38.6 ± 3.4 g, p < 0.001). Anabolic/catabolic signaling was assessed in gastrocnemius muscle. Espindolol decreased proteasome and caspase‐3 proteolytic activities by approximately 50 % (all p < 0.05). Western blotting showed a reduced expression of key catabolic regulators, including NFκB, MuRF1, and LC‐3 (all p < 0.01). The 50‐ and 26‐kDa forms of myostatin were downregulated fivefold and 20‐fold, respectively (both p < 0.001). Moreover, 4E‐BP‐1 was reduced fivefold ( p < 0.01), while phospho‐PI3K was upregulated fivefold ( p < 0.001), although Akt expression and phosphorylation were lower compared to placebo (all p < 0.05). No regulation of p38 and expression of ERK1/2 were observed, while phosphorylation of p38 was reduced (−54 %, p < 0.001) and ERK1/2 was increased (115 and 83 %, respectively, both p < 0.01). Espindolol did not affect cardiac function (echocardiography) or clinical plasma parameters. Conclusion Espindolol reversed the effects of aging/sarcopenia, particularly loss of muscle mass and increased fat mass. Thus, espindolol is an attractive candidate drug for the treatment of sarcopenia patients. Electronic supplementary material The online version of this article (doi:10.1007/s13539‐013‐0125‐7) contains supplementary material.