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.

  • Original Article
  • Published:

Regulation of LKB1 expression by sex hormones in adipocytes

International Journal of Obesity volume 36, pages 982–985 (2012)Cite this article

Abstract

Objective:

In the adipose tissue, activation of AMP-activated protein kinase (AMPK) by phosphorylation favours local fatty acid oxidation and inhibition of lipogenesis. We have previously shown that the potent androgen dihydrotestosterone (DHT) can inhibit phosphorylation of AMPK in adipose tissue and 3T3-L1 adipocytes in a dose-dependent manner. This negative effect of DHT was reversed by oestrogen treatment. The purpose of this current study was to determine the underlying mechanisms whereby androgens and oestrogens can regulate AMPK phosphorylation in adipocytes, and whether this mechanism is receptor dependent.

Results:

Phosphorylation of AMPK was assessed by western blot in cells treated for 24 h with testosterone or DHT (1–1000 nM). Testosterone and DHT significantly inhibited basal phosphorylation of AMPK. Addition of the androgen receptor antagonist Flutamide (1 μM) to the media reversed the negative effect of testosterone and DHT by returning AMPK phosphorylation levels to those of basal. To further dissect the mechanism underlying AMPK inhibition by testosterone or DHT, we examined the mRNA expression of the upstream activator of AMPK, namely LKB1. Testosterone and DHT treatment of murine 3T3-L1 or human SGBS adipocytes for 24 h significantly decreased the mRNA expression of LKB1. In contrast, 17β-estradiol treatment increased LKB1 mRNA, an effect mediated by oestrogen receptor alpha.

Conclusion:

We conclude that regulation of AMPK phosphorylation by androgens and oestrogens is receptor-dependent, and demonstrate for the first time that LKB1 is regulated by sex hormones in adipocytes.

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
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Poehlman ET . Transversing the menopause: change in energy expenditure and body composition. Coron Artery Dis 2005; 16: 511.

    Article  Google Scholar 

  2. Liu YM, Ding JZ, Trudy TL, Longenecker JC, Nieto FJ, Golden SH et al. Relative androgen excess and increased cardiovascular risk after menopause: a hypothesized relation. Am J Epidemiol 2001; 154: 489–494.

    Article  CAS  Google Scholar 

  3. McInnes KJ, Corbould A, Simpson ER, Jones ME . Regulation of adenosine 5′,monophosphate-activated protein kinase and lipogenesis by androgens contributes to visceral obesity in an estrogen-deficient state. Endocrinol 2006; 147: 5907–5913.

    Article  CAS  Google Scholar 

  4. Fisher CR, Graves KH, Parlow AF, Simpson ER . Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene. Proc Natl Acad Sci USA 1998; 95: 6965–6970.

    Article  CAS  Google Scholar 

  5. Simpson ER, Misso M, Hewitt KN, Hill RA, Boon WC, Jones ME et al. Estrogen—the good, the bad, and the unexpected. Endocr Rev 2005; 26: 322–330.

    Article  CAS  Google Scholar 

  6. Jones MEE, Boon WC, McInnes K, Maffei L, Carani C, Simpson ER . Recognizing rare disorders: aromatase deficiency. Nat Clin Pract Endocrinol Metab 2007; 3: 414–421.

    Article  CAS  Google Scholar 

  7. Woods A, Johnstone SR, Dickerson K, Leiper FC, Fryer LGD, Neumann D et al. LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 2003; 13: 2004–2008.

    Article  CAS  Google Scholar 

  8. Brown KA, McInnes KJ, Hunger NI, Oakhill JS, Steinberg GR, Simpson ER . Subcellular localization of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 provides a link between obesity and breast cancer in postmenopausal women. Cancer Res 2009; 69: 5392–5399.

    Article  CAS  Google Scholar 

  9. Barros RPA, Gabbi C, Morani A, Warner M, Gustafsson JA . Participation of ER alpha and ER beta in glucose homeostasis in skeletal muscle and white adipose tissue. Am J Physiol-Endocrinol Metabol 2009; 297: E124–E133.

    Article  CAS  Google Scholar 

  10. Yu IC, Lin HY, Liu NC, Wang RS, Sparks JD, Yeh S et al. Hyperleptinemia without obesity in male mice lacking androgen receptor in adipose tissue. Endocrinol 2008; 149: 2361–2368.

    Article  CAS  Google Scholar 

  11. Pasquali R . Obesity and androgens: facts and perspectives. Fertil Steril 2006; 85: 1319–1340.

    Article  CAS  Google Scholar 

  12. Alessi DR, Sakamoto K, Bayascas JR . LKB1-dependent signaling pathways. Annu Rev Biochem 2006; 75: 137–163.

    Article  CAS  Google Scholar 

  13. Carling D . LKB1: a sweet side to Peutz-Jeghers syndrome? Trends Mol Med 2006; 12: 144–147.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the Victorian Breast Cancer Research Consortium Inc., NHMRC Project Grant No. 494819 and Program Grant No. 494802. KJM supported by an RD Lawrence Personal Fellowship from Diabetes UK. KAB is supported by an NHMRC Career Development Award. ERS is supported by an NHMRC Senior Principal Research Fellowship.

Author information

Author notes

  1. K J McInnes and K A Brown: These authors contributed equally to this work.

Authors and Affiliations

  1. Endocrinology Unit, BHF/University Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, Scotland, UK

    K J McInnes

  2. Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia

    K A Brown, N I Hunger & E R Simpson

  3. Department of Physiology, Monash University, Clayton, Victoria, Australia

    K A Brown

  4. Department of Biochemistry, Monash University, Clayton, Victoria, Australia

    E R Simpson

Authors
  1. K J McInnes
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K A Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N I Hunger
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E R Simpson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K J McInnes.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McInnes, K., Brown, K., Hunger, N. et al. Regulation of LKB1 expression by sex hormones in adipocytes. Int J Obes 36, 982–985 (2012). https://doi.org/10.1038/ijo.2011.172

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2011.172

Keywords

This article is cited by

Search

Advanced search

Quick links