Persistent lipolytic effect of exogenous growth hormone during caloric restriction

In previous studies in which obese volunteers were calorically restricted to 24, 18, or 12 kcal/kg of ideal body weight (IBW) per day, we observed that the growth-hormone-induced acceleration of body fat loss was variable and that the severity of caloric restriction modulated the magnitude of fat loss and the anabolic response to growth hormone. The present study was undertaken to characterize the effects of caloric restriction to 15 kcal/kg IBW per day on the metabolic response to growth hormone and to determine whether acceleration of body fat loss by growth hormone could be reproduced under conditions predicted to be optimal.

Eleven obese subjects were studied during two 38-day periods of caloric restriction. During one of these periods they received injections of growth hormone, 0.05 mg/kg IBW, for 28 days. Measurements of nitrogen balance, body fat content, insulin like growth factor I (IGF-I), free fatty acids, and glycerol concentrations were performed.

Growth hormone injections caused an approximate 2.5-fold increase in IGF-I concentrations so that the mean IGF-I concentration was significantly greater during the injections than during diet alone (growth hormone 69.3 +/- 29.3 nmol/L; diet alone 26.6 +/- 7.6 nmol/L; P < 0.001). Growth hormone also caused nitrogen sparing, and the mean daily nitrogen balance was significantly greater during the injections (growth hormone 36.9 +/- 121.1 mmol/day; diet alone -122.3 +/- 125.9 mmol/day; P < 0.001). This nitrogen-sparing response to growth hormone attenuated over the 4 weeks of the injections. Growth hormone had a persistent lipolytic effect manifested by increases in glycerol concentrations, and body fat loss was greater during injections than during diet alone (fraction of weight lost as fat during injections 0.77 +/- 0.07; diet alone 0.63 +/- 0.06; P < 0.001).

We conclude that growth hormone exerts anabolic effects that attenuate over time during caloric restriction but maintains its lipolytic effect despite hyperinsulinism and results in accelerated fat loss.