Skip to main content
SpringerLink
Log in

Ghrelin: Impact on Muscle Energy Metabolism in Sepsis

  • Published:
International Journal of Peptide Research and Therapeutics Aims and scope Submit manuscript

Abstract

We investigated the effects of exogenous ghrelin on energy levels and tissue histology in skeletal muscle in experimentally lipopolysaccharide (LPS) induced septic rats. Male Wistar albino rats 200–250 g were separated into four groups; Control, LPS (5 mg/kg), Ghrelin (10 nmol/kg i.v.), and ghrelin+LPS. Gastrocnemius muscle tissue was taken and stained using modified Gomori trichrome (MGT), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) and hematoxylin and eosin. In stained sections, histological score value was calculated according to the intensity and the distribution for MGT, SDH and COX stainings. Creatine, creatine phosphate, adenosine triphosphate (ATP), adenosine monophosphate (AMP) levels, and the ratios of AMP/ATP and CreaP/ATP were investigated using high performance liquid chromatography (HPLC) in muscle tissue. Significances between experimental groups were calculated with an analysis of variance (ANOVA) followed by Tukey’s tests. Myopathic changes were seen in the 50% of rats in the LPS group as rounding of muscle fibers and fiber size variation. In the ghrelin+LPS group, ghrelin treatment was reduced damage in skeletal muscle structure. There was no change in creatine or AMP levels between the groups. Ghrelin treatment significantly increased ATP values (P < 0.01) and improved tissue histology in septic rats. Ratios of both AMP/ATP and CreaP/ATP were found increased in the septic group, but there were decreaments in both the ghrelin and ghrelin-treated septic groups. Ghrelin could play an important role in energy balance and muscle morphology in skeletal muscle during sepsis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Albarrán-Zeckler RG, Smith RG (2013) The ghrelin receptors (GHS-R1a and GHS-R1b). Endocr Dev 25:5–15

    Article  PubMed  Google Scholar 

  • Ates G, Ozkok E, Yorulmaz H, Aydin I, Tamer S (2017) Effects of ghrelin on inflammation and oxidative stress parameters in sepsis-induced liver tissue of rat. Asian J Anim Vet Adv 12:17–23.

    Article  Google Scholar 

  • Barazzoni R, Bosutti A., Stebel M et al (2005) Ghrelin regulates mitochondriallipid metabolism gene expression and fat distribution in liver and skeletal muscle. Am J Physiol Endocrinol Metab 288:228–235.

    Article  Google Scholar 

  • Barazzoni R, Zanetti M, Cattin MR et al (2007) Ghrelin enhances in vivo skeletal muscle but not liver AKT signaling in rat. Obesity 15:2614–2623

    Article  CAS  PubMed  Google Scholar 

  • Brealey D, Singer M (2003) Mitochondrial dysfunction in sepsis. Curr Infect Dis Rep 5:365–371

    Article  PubMed  Google Scholar 

  • Callahan LA, Supinski GS (2005) Downregulation of diaphragm electron transport chain and glycolytic enzyme gene expression in sepsis. J Appl Physiol 99:1120–1126

    Article  PubMed  Google Scholar 

  • Chang L, Du JB, Gao LR, Pang YZ, Tang CS (2003) Effect of ghrelin on septic shock in rats. Acta Pharmacol Sin 24(1):45–49

    CAS  PubMed  Google Scholar 

  • Chen HW, Hsu C, Lu TS, Wang SJ, Yang RC (2003) Heat shock pretreatment prevents cardiac mitochondrial dysfunction during sepsis. Shock 20:274–279

    Article  PubMed  Google Scholar 

  • Clark AS, Kelly RA, Mitch WE (1984) Systemic response to thermal injury in rats. Accelerated protein degradation and altered glucose utilization in muscle. J Clin Invest 74:888–897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Engel WK, Cunningham GG (1963) Rapid examinaiıon of muscle tissue an improved trichrome method for fresh-frozen biopsy sections. Neurology 13:919–923

    Article  CAS  PubMed  Google Scholar 

  • Fink MP (2002) Bench-to-bedside review: cytopathic hypoxia. Crit Care 6:491–499

    Article  PubMed  PubMed Central  Google Scholar 

  • Forget AP, Mangalaboyi J, Mordon S et al (2000) Escherichia coli endotoxin reduces cytochrome aa3 redox status in pig skeletal muscle. Crit Care Med 28:3491–3497

    Article  CAS  PubMed  Google Scholar 

  • Fukushima R, Saito H, Inoue T et al (1999) Prophylactic treatment with growth hormone and insulin-like growth factor I improve systemic bacterial clearance and survival in a murine model of burn-induced gut derived sepsis. Burns 25:425–430

    Article  CAS  PubMed  Google Scholar 

  • Giannesini B, Izquierdo M, Le Fur Y et al (2009) Beneficial effects of citrulline malate on skeletal muscle function in endotoxemic rat. Eur J Pharmacol 602(1):143–147

    Article  CAS  PubMed  Google Scholar 

  • Hauptmann S, Klosterhalfen B, Weis J, Mittermeyer C, Kirkpatrick CJ (1994) Skeletal muscle oedema and muscle fibre necrosis during septic shock. Observations with a porcine septic shock model. Virchows Arch 424:653–659

    Article  CAS  PubMed  Google Scholar 

  • Hobler SC, Tiao G, Fischer JE, Monaco J, Hasselgren PO (1998) The sepsis-induced increase in muscle proteolysis is blocked by specific proteasome inhibitors. Am J Physiol 274:30–37

    Google Scholar 

  • Kola B (2008) Role of AMP-activated protein kinase in the control of appetite. J Neuroendocrinol 20:942–951

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Langhans C, Weber-Carstens S, Schmidt F et al (2014) Inflammation-induced acute phase response in skeletal muscle and critical illness myopathy. PLoS ONE 9:92048

    Article  Google Scholar 

  • Lara TM, Wong MS, Rounds J, Robınson MK, Wilmore DW, Jacobs DO (1998) Skeletal muscle phosphocreatine depletion depresses myocellular energy status during sepsis. Arch Surg 133:1316–1321

    Article  CAS  PubMed  Google Scholar 

  • Nagaya N, Uematsu M, Kojima M et al (2001) Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation 104:2034–2038

    Article  CAS  PubMed  Google Scholar 

  • Rocheteau P, Chatre L, Briand D et al (2015) Sepsis induces long-term metabolic and mitochondrial muscle stem cell dysfunction amenable by mesenchymal stem cell therapy. Nat Commun 6:10145

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shellvold OFM, Jnge P, Aarstad K (1986) High performance liquid chromatography: a rapid isocratic method for determination of creatine compounds anda denine nucleotides in the myocardial tissues. J Mol Cell Cardiol 18:517–527

    Article  Google Scholar 

  • Singer M (2008) Cellular dysfunction in sepsis. Clin Chest Med 29:655–660

    Article  PubMed  Google Scholar 

  • Takiguchi S, Murakami K, Yanagimoto Y et al (2015) Clinical application of ghrelin in the field of surgery. Surg Today 45(7):801–807

    Article  CAS  PubMed  Google Scholar 

  • Tanji K, Bonilla E (2008) Light microscopic methods to visualize mitochondria on tissue sections. Methods 46:274–280

    Article  CAS  PubMed  Google Scholar 

  • Tiao G, Fagan JM, Samuels N et al (1994) Sepsis stimulates nonlysosomal energy-dependent proteolysis and increases ubiquitin mRNA levels in rat skeletal muscle. J Clin Invest 94:2255–2264

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tiao G, Hobler S, Wang JJ et al (1997) Sepsis is associated with increased mRNAs of the ubiquitin-proteasome proteolytic pathway in human skeletal muscle. J Clin Invest 99:163–168

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Trumbeckaite S, Opalka JR, Neuhof C, Zierz S, Gellerich FN (2001) Different sensitivity of rabbit heart and skeletal muscle to endotoxin-induced impairment of mitochondrial function. Eur J Biochem 268:1422–1429

    Article  CAS  PubMed  Google Scholar 

  • Vanasco V, Cimolai MC, Evelson P, Alvarez S (2008) The oxidative stress and the mitochondrial dysfunction caused by endotoxemia are prevented by alphalipoic acid. Free Radic Res 42:815–823

    Article  CAS  PubMed  Google Scholar 

  • Zheng X, Xu M, Fang Q. (2014) Role of AMPK α in skeletal muscle glycometabolism regulation and adaptation in relation to sepsis. Biomed Res Int 2014:390760

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Our study was granted from Istanbul University Research Projects (Projects No: 42363). We would like also thank Mr. David F Chapman for editing the English in this article. Also we would like to the selection of muscle images to Dr Gokcen Unverengil and the stainings of muscle sections to Ms. Hatice Tasli.

Author information

Authors and Affiliations

  1. Faculty of Medicine, Halic University, Sütlüce Mah. İmrahor Cad. No: 82 Beyoğlu, Istanbul, Turkey

    Hatice Yorulmaz

  2. Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey

    Elif Ozkok

  3. Department of Physiology, Istanbul University, Istanbul, Turkey

    Gulten Ates & Sule Tamer

  4. Department of Physiology, Faculty of Medicine, Yeniyuzyil University, Istanbul, Turkey

    Gulten Ates

  5. Department of Chemical Oceanography, Institute of Marine Sciences and Management, Istanbul University, Istanbul, Turkey

    Abdullah Aksu & Nuray Balkıs

Authors
  1. Hatice Yorulmaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elif Ozkok
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gulten Ates
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abdullah Aksu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Nuray Balkıs
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sule Tamer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hatice Yorulmaz.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Yorulmaz, H., Ozkok, E., Ates, G. et al. Ghrelin: Impact on Muscle Energy Metabolism in Sepsis. Int J Pept Res Ther 24, 259–264 (2018). https://doi.org/10.1007/s10989-017-9610-8

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10989-017-9610-8

Keywords

Search

Navigation