Submission Number: ELE-4-21-4

Abstract Number: 186

LEPTIN GENE THERAPY REDUCES FOOD INTAKE AND BODY WEIGHT WITHOUT AFFECTING ONSET OF PUBERTY AND REPRODUCTIVE CYCLES.

E Beretta ¹, M Dube ², H Dhillon ^1,2, V Prima ³, S Zolotukhin ³, N Muzyczka ³, PS Kalra ^1,2 and SP Kalra* ^1,2

Dept of Neuroscience, College of Medicine, Gainesville, FL ¹
Dept of Physiology, College of Medicine, Gainesville, FL ²
Dept of Molecular Genetics and Microbiology, College of Medicine, Gainesville, FL ³

Abstract:
Leptin, the adipocyte hormone, suppresses food intake and body weight gain by its action in the hypothalamus. A recombinant adeno-associated virus encoding leptin (rAAV-Ob) was generated and injected intracerebroventricularly (6 x 10¹⁰ particles in 3 l) into 24 day-old female Sprague-Dawley rats. The control groups consisted of a) rats injected icv with rAAV-UF5 (control vector) and b) unoperated, untreated rats. Rats were maintained on ad-libitum rat chow and water. Food intake and body weight were monitored for 6 months. The results showed that during the pubertal period through day 44, rAAV-lep-Ob-treated rats consumed 26.9% less and 22.8% less during the post-pubertal period through day 180. Body weight gain was accordingly reduced in these rats (rAAV-Ob: 114.3 9.2 g; rAAV-UF5: 206.0 4.1 g). Despite this marked suppression of caloric intake and weight gain, the age at vaginal opeing of rAAV-Ob-treated rats was not different from that of control rats (rAAV-Ob: 39.9 0.6 days; rAAV-UF5: 39.0 0.9 days; untreated control: 38.6 0.8 days). To examine the effects on estrous cycles, vaginal smears were recorded between days 54-70. All groups exhibited a similar number of estrous cycles of 4-5 day duration (rAAV-Ob: 3.1 0.2; rAAV-UF5: 2.9 0.2; untreated controls: 2.4 0.2). These results show, for the first time, that leptin gene therapy administered prepubertally suppressed food intake and weight gain without altering either the onset of puberty or reproductive cycles in adult life. Consequently, centrally administered leptin gene therapy is a viable therapy to diminish appetite and maintain a lean phenotype for long periods without disrupting the neuroendocrine control of puberty and reproductive cycles. (Supported by NIH HD-08634).

Keywords: Gene Therapy, Leptin and Reproduction

This abstract is being presented at: 8:00 AM in session:
Nutrition and Reproduction