Increased leptin resistance as rats grow to maturity.

Three or eight-month-old Sprague-Dawley rats were treated intracerebroventricularly (ICV) with 5 microg of rat leptin/d for 5 days to determine the effect of age on leptin's actions in ingestive behavior, adipose tissue cellularity, organ weights, body composition, and blood metabolite profile. Effects of leptin on food intake were greater in young immature rats (22.0 vs. 5.7 g/d) than in mature rats (17.4 vs. 9.3 g/d) with a leptin x age interaction (P< 0.01). Leptin results in body weight loss (P < 0.001) by 19% and 9% in young and mature rats, respectively. Water intake was reduced by leptin treatment only in young animals (P< 0.001). The decrease in carcass weight by leptin treatment (P < 0.001) was observed in both young (22%) and mature rats (9%). Leptin treatment greatly reduced retroperitoneal (0.82 vs. 0.11 g, P < 0.05) and epididymal fat weight (1.90 vs. 0.48 g, P < 0.003), associated with a reduction in total adipocyte cell number, DNA content, and cellular volume in young rats; however, there were no effects of leptin in the mature rats. In addition, young rats also displayed a 60% loss of carcass lipid content. An increase in serum fatty acid levels by leptin treatment was observed also only in young rats (P< 0.001). An interaction of leptin by age that was observed for the reduction of serum glucose levels by leptin treatment (P < 0.04) further indicated that mature rats showed a leptin insensitivity compared to young rats. In summary, the data suggest that normal rats become resistant to leptin as they age.