PERSISTENT LIPOLYTIC EFFECT OF EXOGENOUS GROWTH-HORMONE DURING CALORIC RESTRICTION

PURPOSE: In previous studies in which obese volunteers were caloricall y restricted to 24, 18, or 12 kcal/kg of ideal body weight (IBW) per d ay, we observed that the growth-hormone-induced acceleration of body f at loss was variable and that the severity of caloric restriction modu lated the magnitude of fat loss and the anabolic response to growth ho rmone. The present study was undertaken to characterize the effects of caloric restriction to 15 kcal/kg IBW per day on the metabolic respon ses to growth hormone and to determine whether acceleration of body fa t loss by growth hormone could be reproduced under conditions predicte d to be optimal. PATIENTS AND METHODS: Eleven obese subjects were stud ied during two 38-day periods of caloric restriction. During one of th ese periods they received injections of growth hormone, 0.05 mg/kg IBW , for 28 days. Measurements of nitrogen balance, body fat content, ins ulin like growth factor I (IGF-I), free fatty acids, and glycerol conc entrations were performed. RESULTS: Growth hormone injections caused a n approximate 2.5-fold increase in IGF-I concentrations so that the me an IGF-I concentration was significantly greater during the injections than during diet alone (growth hormone 69.3 +/- 29.3 nmol/L; diet alo ne 26.6 +/- 7.6 nmol/L; P <0.001). Growth hormone also caused nitrogen sparing, and the mean daily nitrogen balance was significantly greate r 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 resp onse to growth hormone attenuated over the 4 weeks of the injections. Growth hormone had a persistent lipolytic effect manifested by increas es in glycerol concentrations, and body fat loss was greater during in jections 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). CONCLU SION: We conclude that growth hormone exerts anabolic effects that att enuate over time during caloric restriction but maintains its lipolyti c effect despite hyperinsulinism and results in accelerated fat loss.