Neuroendocrine consequences of fasting in adult male macaques: Effects of recombinant rhesus macaque leptin infusion

Fasting inhibits the gonadotropic axis and stimulates the corticotropic and somatotropic axes. Since leptin is a product of fat cells that has been im plicated in the control of both reproduction and metabolism, we hypothesize d that the decrease in leptin observed during fasting was responsible for t hese effects on reproductive and metabolic hormones. Recombinant rhesus lep tin (rrhLep) produced in our laboratory was infused (100 mu g/h) into faste d adult male rhesus macaques (6-9 kg) beginning at midnight after the first missed meal and continuing until the end of the study, Bioactive luteinizi ng hormone (LH), testosterone, cortisol and growth hormone (GH) were measur ed in plasma from samples collected at 15-min intervals for the last 15 h ( 42-57 h) of the fast. We analyzed pulsatile LH and GH secretion by deconvol ution analysis and the orderliness of pulsatile LH and GH release by the ap proximate entropy (ApEn) statistic. There was no difference in LH pulse fre quency between control and fasted groups, but there was a significant decre ase in the mean concentration of LH released (7.6 +/- 1.4 ng/ml control vs. 2.7 +/- 0.65 ng/ml fasted) that was not relieved with rrhLep infusions (2. 8 +/- 0.83 ng/ml). Model-free Cluster analysis confirmed these inferences a nd also indicated that the peak height was tower in the fasted (4.6 +/- 1.0 ng/ml) and the fasted + rrhLep (2.85 +/- 1.0 ng/ml) groups compared to con trols (16.3 +/- 1.4 ng/ml). Testosterone levels reflected those of LH. Fast ing resulted in an increase in GH secretory pulse frequency (5.3 +/- 0.95 p ulses/15 h control vs. 12.8 +/- 1.4 pulses/15 h fasted) and this increase w as not affected by rrhLep infusion (12.5 +/- 1.4 pulses/15 h). In addition, fasting also increased the ApEn (decreased the orderliness) of pulsatile G H secretion, and this characteristic was not relieved with rrhLep infusions . Cortisol levels in fasted animals were 2- to 3-fold higher than those obs erved in control studies, and this increase was particularly pronounced at the time when the animals expected their first meal of the day. The increas e in circulating cortisol observed in fasted animals was not affected by rr hLep infusion. Glucose levels at the end of the sampling period were 80 mg/ dl in controls, 48 mg/dl in fasted animals and 58 mg/dl in the fasted + rrh Lep group. Circulating leptin levels averaged 1.2 +/- 0.37 ng/ml in control animals, 0.7 +/- 0.2 ng/ml in fasted animals and 10.1 +/- 5.6 ng/ml in fas ted animals infused with rrhLep. These studies suggest that intravenous rep lacement with homologous leptin does not reverse the acute changes in GH, L H and cortisol secretion observed with fasting in the adult male macaque. C opyright (C) 2000 S. Karger AG, Basel.