Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Short Communication
  • Published:

The impact of glutathione transferase kappa deficiency on adiponectin multimerisation in vivo

International Journal of Obesity volume 36, pages 1366–1369 (2012)Cite this article

Subjects

Abstract

Glutathione transferase Kappa (GSTK1-1) also termed disulfide bond-forming oxidoreductase A-like protein (DsbA-L) has been implicated in the post-translational multimerization of adiponectin and has been negatively correlated with obesity in mice and humans. We investigated adiponectin in Gstk1−/− mice and surprisingly found no difference in the levels of total serum adiponectin or the level of high molecular weight (HMW) multimers when compared with normal controls. Non-reducing SDS-polyacrylamide gel electrophoresis and western blotting also showed a similar distribution of low, middle and HMW multimers in normal and Gstk1−/− mice. Variation in adiponectin has been correlated with glucose tolerance and with the levels of phosphorylated AMP-kinase but we found similar glucose tolerance and similar levels of phospho 5-AMP-activated protein kinase in normal and Gstk1−/− mice. Consequently, our findings suggest that GSTK1-1 is not absolutely required for adiponectin multimerization in vivo and alternate pathways may be activated in GSTK1-1 deficiency.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Wang Y, Lam KS, Yau MH, Xu A . Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J 2008; 409: 623–633.

    Article  CAS  Google Scholar 

  2. Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 2001; 86: 1930–1935.

    Article  CAS  Google Scholar 

  3. Yatagai T, Nagasaka S, Taniguchi A, Fukushima M, Nakamura T, Kuroe A et al. Hypoadiponectinemia is associated with visceral fat accumulation and insulin resistance in Japanese men with type 2 diabetes mellitus. Metabolism 2003; 52: 1274–1278.

    Article  CAS  Google Scholar 

  4. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K . Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006; 116: 1784–1792.

    Article  CAS  Google Scholar 

  5. Ohashi K, Kihara S, Ouchi N, Kumada M, Fujita K, Hiuge A et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension 2006; 47: 1108–1116.

    Article  CAS  Google Scholar 

  6. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 2002; 106: 2767–2770.

    Article  CAS  Google Scholar 

  7. Xu A, Wang Y, Keshaw H, Xu LY, Lam KS, Cooper GJ . The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice. J Clin Invest 2003; 112: 91–100.

    Article  CAS  Google Scholar 

  8. Pajvani UB, Hawkins M, Combs TP, Rajala MW, Doebber T, Berger JP et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Biol Chem 2004; 279: 12152–12162.

    Article  CAS  Google Scholar 

  9. Liu M, Zhou L, Xu A, Lam KS, Wetzel MD, Xiang R et al. A disulfide-bond A oxidoreductase-like protein (DsbA-L) regulates adiponectin multimerization. Proc Natl Acad Sci USA 2008; 105: 18302–18307.

    Article  CAS  Google Scholar 

  10. Thomson RE, Bigley AL, Foster JR, Jowsey IR, Elcombe CR, Orton TC et al. Tissue-specific expression and subcellular distribution of murine glutathione S-transferase class kappa. J Histochem Cytochem 2004; 52: 653–662.

    Article  CAS  Google Scholar 

  11. Morel F, Rauch C, Petit E, Piton A, Theret N, Coles B et al. Gene and protein characterization of the human glutathione S-transferase kappa and evidence for a peroxisomal localization. J Biol Chem 2004; 279: 16246–16253.

    Article  CAS  Google Scholar 

  12. Morel F, Aninat C . The glutathione transferase kappa family. Drug Metab Rev 2011; 43: 281–291.

    Article  CAS  Google Scholar 

  13. Robinson A, Huttley GA, Booth HS, Board PG . Modelling and bioinformatics studies of the human Kappa class glutathione transferase predict a novel third glutathione transferase family with homology to prokaryotic 2-hydroxychromene-2-carboxylate (HCCA) isomerases. Biochem J 2004; 379 (Pt 3): 541–552.

    Article  CAS  Google Scholar 

  14. Ladner JE, Parsons JF, Rife CL, Gilliland GL, Armstrong RN . Parallel evolutionary pathways for glutathione transferases: structure and mechanism of the mitochondrial class kappa enzyme rGSTK1-1. Biochemistry 2004; 43: 352–361.

    Article  CAS  Google Scholar 

  15. Blackburn AC, Coggan M, Shield AJ, Cappello J, Theodoratos A, Murray TP et al. Glutathione transferase kappa deficiency causes glomerular nephropathy without overt oxidative stress. Lab Invest 2011; 91: 1572–1583.

    Article  CAS  Google Scholar 

  16. Sharma K, Ramachandrarao S, Qiu G, Usui HK, Zhu Y, Dunn SR et al. Adiponectin regulates albuminuria and podocyte function in mice. J Clin Invest 2008; 118: 1645–1656.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Ebinuma H, Miida T, Yamauchi T, Hada Y, Hara K, Kubota N et al. Improved ELISA for selective measurement of adiponectin multimers and identification of adiponectin in human cerebrospinal fluid. Clin Chem 2007; 53: 1541–1544.

    Article  CAS  Google Scholar 

  18. Bullen Jr JW, Bluher S, Kelesidis T, Mantzoros CS . Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice. Am J Physiol Endocrinol Metab 2007; 292: E1079–E1086.

    Article  CAS  Google Scholar 

  19. Yamauchi T, Kamon J, Minokoshi Y, Ito Y, Waki H, Uchida S et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8: 1288–1295.

    Article  CAS  Google Scholar 

  20. Kadowaki T, Yamauchi T, Kubota N . The physiological and pathophysiological role of adiponectin and adiponectin receptors in the peripheral tissues and CNS. FEBS Lett 2008; 582: 74–80.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

These studies were undertaken with the financial support of NHMRC Grant 418071, an NHMRC RD Wright Fellowship to AB and an NHMRC Australian Biomedical (Peter Doherty) Fellowship to CL.

Author information

Authors and Affiliations

  1. The John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia

    A Theodoratos, A C Blackburn, M Coggan, J Cappello, K I Matthaei & P G Board

  2. ANU Medical School, The Canberra Hospital, Canberra, ACT, Australia

    C Z Larter

Authors
  1. A Theodoratos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A C Blackburn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Coggan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J Cappello
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Z Larter
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K I Matthaei
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P G Board
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to P G Board.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Theodoratos, A., Blackburn, A., Coggan, M. et al. The impact of glutathione transferase kappa deficiency on adiponectin multimerisation in vivo. Int J Obes 36, 1366–1369 (2012). https://doi.org/10.1038/ijo.2011.267

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2011.267

Keywords

This article is cited by

Search

Advanced search

Quick links