Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression of myostatin in a rat heart failure model

Karsten Lenk, Sandra Palus, Robert Schur, Rakesh Datta, Jesse Dong, Michael D. Culler, Stefan Anker, Jochen Springer, Gerhard Schuler, Volker Adams

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Background: In chronic heart failure (CHF), cachexia is a hallmark of the terminal stage of this disease and is associated with a severely reduced quality of life and poor prognosis. Therapeutic options are currently not available. Ghrelin and its analogues BIM-28125 and BIM-28131 (now known as RM-131) have been shown to increase weight in a rat model of CHF. It has been further demonstrated that the expression of myostatin, a negative regulator of skeletal muscle mass, is increased in CHF. The aim of the study was to investigate the influence of ghrelin or its analogues on myostatin in CHF. Methods: In an animal model of CHF, Sprague-Dawley rats received either ghrelin or two ghrelin analogues BIM-28125 and BIM-28131 in two different concentrations (50 and 500 nmol/kg/day) compared to placebo. The compounds were delivered using osmotic mini pumps. The expression of myostatin was analyzed in skeletal muscle by RT-PCR and Western blot, and muscle mass of gastrocnemius muscle was measured. The plasma levels of tumor necrosis factor alpha (TNF-α) were measured. Results: The relative weight of the gastrocnemius muscle of the sham-operated group was significantly increased compared to placebo-treated CHF rats. The application of ghrelin analogue BIM-28125 and BIM-28131 in their higher concentrations led to a significant reduction in myostatin mRNA expression in comparison to placebo. Myostatin protein expression was significantly reduced in both concentrations of ghrelin and BIM-28131 and in the lower concentration of BIM-28125. The increase of TNF-α plasma concentration in the CHF-animals could be abolished by all used substances. Conclusions: In an animal model of CHF, the expression of myostatin is significantly reduced in the skeletal muscle after application of ghrelin and most concentrations of its analogues BIM-28125 and BIM-28131 possibly due to anti-inflammatory effects.

Original languageEnglish
Pages (from-to)63-69
Number of pages7
JournalJournal of Cachexia, Sarcopenia and Muscle
Volume4
Issue number1
DOIs
Publication statusPublished - 2013

Fingerprint

Myostatin
Ghrelin
Heart Failure
Skeletal Muscle
Placebos
Animal Models
Tumor Necrosis Factor-alpha
Weights and Measures
Cachexia
BIM-28125
relamorelin
Sprague Dawley Rats
Anti-Inflammatory Agents
Western Blotting
Quality of Life
Muscles
Polymerase Chain Reaction
Messenger RNA

Keywords

  • Cachexia
  • Chronic heart failure
  • Ghrelin
  • Muscle wasting
  • Myostatin
  • TNF-α

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physiology (medical)

Cite this

Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression of myostatin in a rat heart failure model. / Lenk, Karsten; Palus, Sandra; Schur, Robert; Datta, Rakesh; Dong, Jesse; Culler, Michael D.; Anker, Stefan; Springer, Jochen; Schuler, Gerhard; Adams, Volker.

In: Journal of Cachexia, Sarcopenia and Muscle, Vol. 4, No. 1, 2013, p. 63-69.

Research output: Contribution to journalArticle

Lenk, K, Palus, S, Schur, R, Datta, R, Dong, J, Culler, MD, Anker, S, Springer, J, Schuler, G & Adams, V 2013, 'Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression of myostatin in a rat heart failure model', Journal of Cachexia, Sarcopenia and Muscle, vol. 4, no. 1, pp. 63-69. https://doi.org/10.1007/s13539-012-0085-3
Lenk, Karsten ; Palus, Sandra ; Schur, Robert ; Datta, Rakesh ; Dong, Jesse ; Culler, Michael D. ; Anker, Stefan ; Springer, Jochen ; Schuler, Gerhard ; Adams, Volker. / Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression of myostatin in a rat heart failure model. In: Journal of Cachexia, Sarcopenia and Muscle. 2013 ; Vol. 4, No. 1. pp. 63-69.
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T1 - Effect of ghrelin and its analogues, BIM-28131 and BIM-28125, on the expression of myostatin in a rat heart failure model

AU - Lenk, Karsten

AU - Palus, Sandra

AU - Schur, Robert

AU - Datta, Rakesh

AU - Dong, Jesse

AU - Culler, Michael D.

AU - Anker, Stefan

AU - Springer, Jochen

AU - Schuler, Gerhard

AU - Adams, Volker

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N2 - Background: In chronic heart failure (CHF), cachexia is a hallmark of the terminal stage of this disease and is associated with a severely reduced quality of life and poor prognosis. Therapeutic options are currently not available. Ghrelin and its analogues BIM-28125 and BIM-28131 (now known as RM-131) have been shown to increase weight in a rat model of CHF. It has been further demonstrated that the expression of myostatin, a negative regulator of skeletal muscle mass, is increased in CHF. The aim of the study was to investigate the influence of ghrelin or its analogues on myostatin in CHF. Methods: In an animal model of CHF, Sprague-Dawley rats received either ghrelin or two ghrelin analogues BIM-28125 and BIM-28131 in two different concentrations (50 and 500 nmol/kg/day) compared to placebo. The compounds were delivered using osmotic mini pumps. The expression of myostatin was analyzed in skeletal muscle by RT-PCR and Western blot, and muscle mass of gastrocnemius muscle was measured. The plasma levels of tumor necrosis factor alpha (TNF-α) were measured. Results: The relative weight of the gastrocnemius muscle of the sham-operated group was significantly increased compared to placebo-treated CHF rats. The application of ghrelin analogue BIM-28125 and BIM-28131 in their higher concentrations led to a significant reduction in myostatin mRNA expression in comparison to placebo. Myostatin protein expression was significantly reduced in both concentrations of ghrelin and BIM-28131 and in the lower concentration of BIM-28125. The increase of TNF-α plasma concentration in the CHF-animals could be abolished by all used substances. Conclusions: In an animal model of CHF, the expression of myostatin is significantly reduced in the skeletal muscle after application of ghrelin and most concentrations of its analogues BIM-28125 and BIM-28131 possibly due to anti-inflammatory effects.

AB - Background: In chronic heart failure (CHF), cachexia is a hallmark of the terminal stage of this disease and is associated with a severely reduced quality of life and poor prognosis. Therapeutic options are currently not available. Ghrelin and its analogues BIM-28125 and BIM-28131 (now known as RM-131) have been shown to increase weight in a rat model of CHF. It has been further demonstrated that the expression of myostatin, a negative regulator of skeletal muscle mass, is increased in CHF. The aim of the study was to investigate the influence of ghrelin or its analogues on myostatin in CHF. Methods: In an animal model of CHF, Sprague-Dawley rats received either ghrelin or two ghrelin analogues BIM-28125 and BIM-28131 in two different concentrations (50 and 500 nmol/kg/day) compared to placebo. The compounds were delivered using osmotic mini pumps. The expression of myostatin was analyzed in skeletal muscle by RT-PCR and Western blot, and muscle mass of gastrocnemius muscle was measured. The plasma levels of tumor necrosis factor alpha (TNF-α) were measured. Results: The relative weight of the gastrocnemius muscle of the sham-operated group was significantly increased compared to placebo-treated CHF rats. The application of ghrelin analogue BIM-28125 and BIM-28131 in their higher concentrations led to a significant reduction in myostatin mRNA expression in comparison to placebo. Myostatin protein expression was significantly reduced in both concentrations of ghrelin and BIM-28131 and in the lower concentration of BIM-28125. The increase of TNF-α plasma concentration in the CHF-animals could be abolished by all used substances. Conclusions: In an animal model of CHF, the expression of myostatin is significantly reduced in the skeletal muscle after application of ghrelin and most concentrations of its analogues BIM-28125 and BIM-28131 possibly due to anti-inflammatory effects.

KW - Cachexia

KW - Chronic heart failure

KW - Ghrelin

KW - Muscle wasting

KW - Myostatin

KW - TNF-α

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