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.

  • Letter to the Editor
  • Published:

Dopamine D2/D3 receptor availability in genetically leptin-deficient patients after long-term leptin replacement

Molecular Psychiatry volume 17, pages 352–353 (2012)Cite this article

The adipocyte-derived hormone, leptin, which plays a principal role in regulating feeding behavior and energy expenditure, modulates central dopamine systems at multiple levels.1, 2, 3 In ob/ob mice, which have a genetic mutation that renders them leptin-deficient, leptin administration was shown to increase dopamine D2/D3 receptor availability in the nucleus accumbens (NAC) by 21% and in the caudate putamen by 29%.2 We now show that in congenitally leptin-deficient humans with an analogous mutation, resumption of leptin treatment, after long-term replacement and short-term removal, does not significantly increase striatal D2/D3 receptor availability.

Three leptin-deficient patients (32-year-old male A, 39- and 44-year-old females B and C, respectively) from a family in Turkey and 16 age- and sex-matched healthy control subjects (6 men, 10 women: mean age=35.3, s.d.=8.7) were tested. Patients have a rare, recessive, missense mutation in the ob gene. They had been treated daily with recombinant methionyl human leptin replacement (r-metHuLeptin; Amylin Pharmaceuticals, San Diego, CA, USA) for 6 years at the time of this study. As described previously, the treatment substantially normalized eating behavior, weight and endocrine function, reversibly increased cerebral gray matter concentration, and altered the brain response to food-related cues.4, 5, 6, 7, 8, 9

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

Relevant articles

Open Access articles citing this article.

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

References

  1. Opland DM, Leinninger GM, Myers Jr MG . Brain Res 2010; 1350: 65–70.

    Article  CAS  Google Scholar 

  2. Pfaffly J, Michaelides M, Wang GJ, Pessin JE, Volkow ND, Thanos PK . Synapse 2010; 64: 503–510.

    Article  CAS  Google Scholar 

  3. Liu J, Perez SM, Zhang W, Lodge DJ, Lu XY . Mol Psychiatry 2011; 16: 1024–1038.

    Article  CAS  Google Scholar 

  4. Licinio J, Caglayan S, Ozata M, Yildiz BO, de Miranda PB, O′Kirwan F et al. Proc Natl Acad Sci USA 2004; 101: 4531–4536.

    Article  CAS  Google Scholar 

  5. Matochik JA, London ED, Yildiz BO, Ozata M, Caglayan S, DePaoli AM et al. J Clin Endocrinol Metab 2005; 90: 2851–2854.

    Article  CAS  Google Scholar 

  6. Baicy K, London ED, Monterosso J, Wong ML, Delibasi T, Sharma A et al. Proc Natl Acad Sci USA 2007; 104: 18276–18279.

    Article  CAS  Google Scholar 

  7. London ED, Berman SM, Chakrapani S, Delibasi T, Monterosso J, Erol HK et al. J Clin Endocrinol Metab 2011; 96: E1212–E1220.

    Article  CAS  Google Scholar 

  8. Berman SM, Paz-Filho G, Wong ML, Kohno M, Licinio J, London ED (submitted for publication).

  9. Paz-Filho G, Wong ML, Licinio J . Obes Rev 2011; 12: e315–e323.

    Article  CAS  Google Scholar 

  10. Lee B, London ED, Poldrack RA, Farahi J, Nacca A, Monterosso JR et al. J Neurosci 2009; 29: 14734–14740.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by the US National Institutes of Health (NIH) Grants P20DA022539 and R01DA020726 (to EDL); K24RR016996, R01DK058851, and U01GM061394 (to JL); K24RR017365 and R01DK063240 (to M-LW); and the UCLA General Clinical Research Center (NIH Grant M01RR00865 to GS Levy). GP-F, M-LW, and JL were supported by The Australian National University institutional funds.

Author information

Author notes

  1. J Licinio and E D London: These authors contributed equally as senior authors on this project.

Authors and Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences and Semel Institute, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA

    K Ishibashi, S M Berman, B Lee & E D London

  2. Brain Research Institute, University of California-Los Angeles, Los Angeles, CA, USA

    S M Berman & E D London

  3. Department of Translational Medicine, John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia

    G Paz-Filho, C Robertson, M-L Wong & J Licinio

  4. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA, USA

    E D London

  5. Department of Physics, University of California-Irvine, Irvine, CA, USA

    M A Mandelkern

Authors
  1. K Ishibashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S M Berman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G Paz-Filho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C Robertson
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M A Mandelkern
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M-L Wong
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J Licinio
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. E D London
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E D London.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

PowerPoint slides

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ishibashi, K., Berman, S., Paz-Filho, G. et al. Dopamine D2/D3 receptor availability in genetically leptin-deficient patients after long-term leptin replacement. Mol Psychiatry 17, 352–353 (2012). https://doi.org/10.1038/mp.2011.156

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/mp.2011.156

This article is cited by

Search

Advanced search

Quick links