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Erschienen in: Journal of Cachexia, Sarcopenia and Muscle 2/2014

01.06.2014 | Original Article

The anabolic catabolic transforming agent (ACTA) espindolol increases muscle mass and decreases fat mass in old rats

verfasst von: Mareike S. Pötsch, Anika Tschirner, Sandra Palus, Stephan von Haehling, Wolfram Doehner, John Beadle, Andrew J. S. Coats, Stefan D. Anker, Jochen Springer

Erschienen in: Journal of Cachexia, Sarcopenia and Muscle | Ausgabe 2/2014

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Abstract

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.
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Metadaten
Titel
The anabolic catabolic transforming agent (ACTA) espindolol increases muscle mass and decreases fat mass in old rats
verfasst von
Mareike S. Pötsch
Anika Tschirner
Sandra Palus
Stephan von Haehling
Wolfram Doehner
John Beadle
Andrew J. S. Coats
Stefan D. Anker
Jochen Springer
Publikationsdatum
01.06.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cachexia, Sarcopenia and Muscle / Ausgabe 2/2014
Print ISSN: 2190-5991
Elektronische ISSN: 2190-6009
DOI
https://doi.org/10.1007/s13539-013-0125-7

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