Skip to main content
Log in

A prepared anti-MSTN polyclonal antibody reverses insulin resistance of diet-induced obese rats via regulation of PI3K/Akt/mTOR&FoxO1 signal pathways

  • Original Research Paper
  • Published:
Biotechnology Letters Aims and scope Submit manuscript

Abstract

Suppression of myostatin (MSTN) is associated with skeletal muscle atrophy and insulin resistance. However, the mechanisms by which MSTN regulates insulin resistance are not well known. We have explored the signaling pathways through which MSTN regulates insulin resistance in diet-induced obese rats using a polyclonal antibody for MSTN. The anti-MSTN polyclonal antibody significantly improved insulin resistance and whole-body insulin sensitivity, decreased MSTN protein expression in muscle samples by 39 % in diet-induced obese rats. Furthermore, the anti-MSTN polyclonal antibody significantly enhanced PI3K activity (140 %), Akt phosphorylation (86 %), GLUT4 protein expression (23 %), the phosphorylation of mTOR (21 %), and inhibited the phosphorylation of FoxO1 (57 %), but did not affect the phosphorylation of GSK-3β. Thus, suppression of MSTN by the anti-MSTN polyclonal antibody reverses insulin resistance of diet-induced obesity via MSTN/PI3K/Akt/mTOR and MSTN/PI3K/Akt/FoxO1 signaling pathways.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Guo T, Jou W, Chanturiya T, Portas J, Gavrilova O, McPherron AC (2009) Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity. PLoS ONE 4:e4937

    Article  PubMed  PubMed Central  Google Scholar 

  • Hittel D, Axelson M, Sarna N, Shearer J, Huffman K, Kraus W (2010) Myostatin decreases with aerobic exercise and associates with insulin resistance. Med Sci Sport Exerc 42:2023–2029

    Article  CAS  Google Scholar 

  • Kadowaki T, Hara K, Yamauchi T, Terauchi Y, Tobe K, Nagai R (2003) Molecular mechanism of insulin resistance and obesity. Exp Biol Med 228:1111–1117

    CAS  Google Scholar 

  • Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. New Engl J Med 346:393–403

    Article  PubMed  CAS  Google Scholar 

  • Kopelman PG (2000) Obesity as a medical problem. Nature 404:635–643

    PubMed  CAS  Google Scholar 

  • Léger B, Cartoni R, Praz M, Lamon S, Dériaz O, Crettenand A, Gobelet C, Rohmer P, Konzelmann M, Luthi F (2006) Akt signalling through GSK-3β, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol 576:923–933

    Article  PubMed  PubMed Central  Google Scholar 

  • Marchitelli C, Savarese MC, Crisà A, Nardone A, Marsan PA, Valentini A (2003) Double muscling in Marchigiana beef breed is caused by a stop codon in the third exon of myostatin gene. Mamm Genome 14:392–395

    Article  PubMed  CAS  Google Scholar 

  • McPherron AC, Lawler AM, Lee SJ (1997) Regulation of skeletal muscle mass in mice by a new TGF- ß superfamily member. Nature 387:83–90

    Article  PubMed  CAS  Google Scholar 

  • Pallafacchina G, Calabria E, Serrano AL, Kalhovde JM, Schiaffino S (2002) A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. Proc Natl Acad Sci USA 99:9213–9218

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  • Schuelke M, Wagner KR, Stolz LE, Hübner C, Riebel T, Kömen W, Braun T, Tobin JF, Lee S-J (2004) Myostatin mutation associated with gross muscle hypertrophy in a child. N Engl J Med 350:2682–2688

    Article  PubMed  CAS  Google Scholar 

  • Srinivasan K, Patole P, Kaul C, Ramarao P (2004) Reversal of glucose intolerance by pioglitazone in high fat diet-fed rats. Methods Find Exp Clin Pharmacol 26:327–333

    Article  PubMed  CAS  Google Scholar 

  • Tang L, Yan Z, Wan Y, Han W, Zhang Y (2007) Myostatin DNA vaccine increases skeletal muscle mass and endurance in mice. Muscle Nerve 36:342–348

    Article  PubMed  CAS  Google Scholar 

  • van der Horst A, Burgering BM (2007) Stressing the role of FoxO proteins in lifespan and disease. Nat Rev Mol Cell Biol 8:440–450

    Article  PubMed  Google Scholar 

  • Zhao B, Wall RJ, Yang J (2005) Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance. Biochem Biophys Res Commun 337:248–255

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Science Fund for Outstanding Young Investigators (30900710), the Natural Science Foundation of Shaanxi Province, China (2012JM3011), the Innovation Funds of Graduate Programs, SNNU (2012CXS036), and the Fundamental Research Funds for the Central Universities (GK201302042 and GK201402045). We would like to thank all the members of our laboratory for their encouragement and help with this study.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Li-jun Sun.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 10104 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tang, L., Liu, Ct., Wang, Xd. et al. A prepared anti-MSTN polyclonal antibody reverses insulin resistance of diet-induced obese rats via regulation of PI3K/Akt/mTOR&FoxO1 signal pathways. Biotechnol Lett 36, 2417–2423 (2014). https://doi.org/10.1007/s10529-014-1617-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10529-014-1617-z

Keywords

Navigation