Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse (original) (raw)

Gene Therapy volume 5, pages 8–18 (1998)Cite this article

Abstract

We have compared the efficacy of daily injection of recombinant leptin protein (rh-leptin) with adenovirus-mediated delivery of the murine or human leptin gene (Ad-leptin) for treatment of obesity in the obese (ob/ob) mouse model. We demonstrate an improved correction profile for obesity and associated surrogate markers using the adenovirus delivery method. Rate of weight loss and percentage satiety were significantly greater in the mice treated with Ad-leptin. These findings were associated with lower peak serum leptin levels with Ad-leptin (22.9 ± 2.6 ng/ml for the human gene, and 48.9 ± 11.5 ng/ml for the murine gene) compared to rh-leptin (385.2 ± 36.0 ng/ml). (Values are given as mean ± standard error of the mean.) Importantly, rh-leptin and ex vivo-expressed Ad-leptin were equivalently active in a functional cell-based assay. The primary difference in the two therapeutic approaches is the continuous chronic secretion of leptin mediated by gene delivery, versus the intermittent bolus delivery and rapid clearance of the daily injection of rh-leptin protein. Thus, in vivo findings suggest that leptin effects are better achieved at lower steady-state levels, a pharmacological feature attained here by gene therapy. These findings may have implications for the potential use of leptin in the treatment of obesity.

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

Access options

Subscribe to this journal

Receive 6 print issues and online access

$259.00 per year

only $43.17 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

Author information

Authors and Affiliations

  1. Department of Human Genetics, Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA
    MA Morsy, MC Gu, JZ Zhao & CT Caskey
  2. Biometrics Research, Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA
    DJ Holder
  3. Laboratory Animal Resources, Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA
    IT Rogers, WJ Pouch & SL Motzel
  4. Research Resources Administration, Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA
    HJ Klein
  5. Cellular and Molecular Biology, Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA
    SK Gupta & X Liang
  6. Genetics and Molecular Biology, Merck and Co, Inc, WP26A-3000, Sumneytown Pike, West Point, 19486, PA, USA
    MR Tota & CI Rosenblum

Authors

  1. MA Morsy
    You can also search for this author inPubMed Google Scholar
  2. MC Gu
    You can also search for this author inPubMed Google Scholar
  3. JZ Zhao
    You can also search for this author inPubMed Google Scholar
  4. DJ Holder
    You can also search for this author inPubMed Google Scholar
  5. IT Rogers
    You can also search for this author inPubMed Google Scholar
  6. WJ Pouch
    You can also search for this author inPubMed Google Scholar
  7. SL Motzel
    You can also search for this author inPubMed Google Scholar
  8. HJ Klein
    You can also search for this author inPubMed Google Scholar
  9. SK Gupta
    You can also search for this author inPubMed Google Scholar
  10. X Liang
    You can also search for this author inPubMed Google Scholar
  11. MR Tota
    You can also search for this author inPubMed Google Scholar
  12. CI Rosenblum
    You can also search for this author inPubMed Google Scholar
  13. CT Caskey
    You can also search for this author inPubMed Google Scholar

Rights and permissions

About this article

Cite this article

Morsy, M., Gu, M., Zhao, J. et al. Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse.Gene Ther 5, 8–18 (1998). https://doi.org/10.1038/sj.gt.3300565

Download citation

Keywords