Leptin gene therapy and daily protein administration: a comparative study in the ob/ob mouse.

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 Adleptin. 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.

journal_name

Gene Ther

journal_title

Gene therapy

authors

Morsy MA,Gu MC,Zhao JZ,Holder DJ,Rogers IT,Pouch WJ,Motzel SL,Klein HJ,Gupta SK,Liang X,Tota MR,Rosenblum CI,Caskey CT

doi

10.1038/sj.gt.3300565

subject

Has Abstract

pub_date

1998-01-01 00:00:00

pages

8-18

issue

1

eissn

0969-7128

issn

1476-5462

journal_volume

5

pub_type

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