Compared to younger animals, aged male Brown Norway (BN) rats demonstrate increased body fat and serum
insulin, and lower
prepro-neuropeptide Y (ppNPY)
mRNA content in the arcuate nucleus (
ARC), and blunted food intake (FI) and
body weight (BW) gain in response to a 72 h fast. Since centrally administered
insulin decreases FI and weight of young rats and inhibits fasting-induced increases of NPY gene expression, we hypothesized that
hyperinsulinemia in old rats contributes to an age-related central dysregulation of energy balance. Young, middle-aged and old BN rats were fed chow with
troglitazone (Trog; 200 mg/kg BW/d) or without
drug for 75 d (Experiment 1) or 66 d (Experiment 2). Rats were then fasted for 72 h, refed for 2 weeks and sacrificed after an overnight fast (Experiment 1) or fasted for 72 h and sacrificed (Experiment 2). Serum
insulin and
leptin were measured from trunk blood and brains were analyzed for ppNPY
mRNA by in situ hybridization. In Experiment 1,
troglitazone treatment resulted in increased post-fast
weight gain, rate of gain and FI in old rats.
Troglitazone decreased serum
insulin by 50% in old rats, while
leptin levels decreased 20-30% in all age groups in Experiment 1. No differences in serum
insulin or
leptin were detectable with
troglitazone treatment in Experiment 2, due to the extreme suppression caused by the 72 h fast.
Troglitazone treatment did not increase
ARC NPY gene expression either after a 72 h fast and re-feeding for 2 weeks (Experiment 1) or immediately after a 72 h fast (Experiment 2). These findings suggest that increased
insulin levels may contribute to age-related impairments of FI and BW regulation. However, improvements in these defects in energy regulation induced by
troglitazone do not appear to result from changes in NPY gene expression, and may be due to alterations in other hypothalamic
neuropeptides that regulate energy balance.