Restoration of fertility in young obese (Lep^ob Lep^ob) male mice with low dose recombinant mouse leptin treatment

OBJECTIVE: We investigated the effects of low-dose leptin treatment on restoration of fertility in young adult male leptin deficient obese mice. EXPERIMENTAL DESIGN AND RESULTS: MMTV-TGF-α Lep^ob Lep^ob mice (8-10 weeks old) were treated with recombinant mouse leptin. In experiment 1, four mice (5 μg/g body weight leptin followed by 2.5 μg/g) lost weight and impregnated females (number of pregnancies/number of females, 3/6, 5/6, 5/10, 4/10). In experiment 2, Leptin-Obese (2.5 μg/g) and Control-Lean mice weighed significantly less than Control-Obese mice. Epididymal pad weights of Control-Obese mice were the heaviest, followed by those of Leptin-Obese mice, and Control-Lean mice were the lightest. Testes weight was greater in Control-Lean vs Control-Obese mice. Leptin-Obese mice had testes weight not significantly different from either control group. Four of five Leptin-Obese mice impregnated females (4/10, 5/10, 2/10, 5/12, 0/10). CONCLUSIONS: These results indicate that low-dosage mouse recombinant leptin treatment restored fertility to young Lep^ob Lep^ob male mice. Although body weights of Leptin-Obese mice were similar to those of lean age-matched mice, epididymal fat pad weights were heavier.