LONG-TERM ADMINISTRATION OF ACIPIMOX POTENTIATES GROWTH-HORMONE RESPONSE TO GROWTH HORMONE-RELEASING HORMONE BY DECREASING SERUM-FREE FATTY-ACID IN OBESITY

Obesity is associated with an impairment of normal growth hormone (GH) secretion and blunted responses to all stimuli. A high plasma free fa tty acid (FFA) level is frequently observed in obesity. FFA participat es in the regulation of pituitary GH secretion. To determine whether t he derangement of GH secretion in obesity is associated with high plas ma FFA levels, tests with GH-releasing hormone (GHRH) and acipimox (AC X), an antilipolytic agent able to decrease FFA, were undertaken in si x obese subjects and seven normal control subjects. In addition, the e ffect of prolonged suppression of FFA level on GH response to GHRH aft er administration of ACX for 1 month was also examined in each of the obese subjects. The GH response in obese subjects (median, 9.1 mu g/L) to GHRH (1-29) (1 mu g/kg intravenously [IV]) was significantly blunt ed as compared with normal control subjects (23.5 mu g/L, P < .05). Ba sal FFA levels were higher in obese subjects (855.2 mu Eq/L) than in n ormal control subjects (514.6 mu Eq/L, P < .05). One-dose ACX (500 mg) decreased FFA levels in both obese and normal subjects: the lowest FF A levels in obese subjects (158.3 mu Eq/L) 2 to 2.5 hours after ACX we re similar to those of normal control subjects (108.7 mu Eq/L). One-do se ACX potentiated GHRH-stimulated GH response in both obese and norma l subjects. GH responses potentiated by ACX in obese subjects (27.1 mu g/L) were similar to GH responses to GHRH in normal control subjects, but lower than in normal subjects treated with ACX plus GHRH (58.5 mu g/L, P < .05). Thereafter, all of the obese subjects were treated wit h ACX for 1 month, after which the ACX plus GHRH tests were repeated. After 1 month of acipimox administration in the obese subjects, GH res ponses (38.8 mu g/L) were significantly higher than those of obese sub jects treated with GHRH and one-dose ACX plus GHRH (P < .05). They wer e similar to GH responses of normal control subjects receiving the one dose ACX plus GHRH test. In conclusion, in obesity the prolonged supp ression of FFA levels induced by long-term administration of ACX poten tiated somatotrope responsiveness, likely acting at the pituitary leve l, suggesting that the duration of FFA suppression had an important re lation to the magnitude of GH response. (C) 1996 by W.B. Saunders Comp any.