ACIPIMOX POTENTIATES GROWTH-HORMONE (GH) RESPONSE TO GH-RELEASING HORMONE WITH OR WITHOUT PYRIDOSTIGMINE BY LOWERING SERUM-FREE FATTY-ACID IN NORMAL AND OBESE SUBJECTS

Obesity is associated with an impairment of normal GH secretion and bl unted responses to all stimuli. Recent reports suggest that increased somatostatinergic activity is the basis for the GH derangement of obes ity. However, the basic mechanism of this alteration is still being de bated. The high plasma free fatty acid (FFA) is frequently observed in obesity. FFA participates in the regulation of pituitary GH secretion . To determine whether the derangement of GH secretion in obesity is a ssociated with high plasma FFA levels, several tests with GHRH with or without pyridostigmine (PYR) and acipimox (ACX), antilipolytic agents able to decrease FFA, were undertaken in six obese and seven normal c ontrol subjects. In obese subjects, the GH response (mean peak +/- SEM : 8.9 +/- 1.1 ug/L) to GHRH-(1-29) (1 ug/kg, iv) was significantly blu nted when compared with the response in normal control subjects (25.7 +/- 1.8 ug/L; P < 0.05). After PYR (120 mg), the response to GHRH was enhanced in the obese subjects (21.4 +/- 4.9 ug/L; P < 0.05) and was s imilar to that of the controls with GHRH only, but remained significan tly reduced compared with controls treated with PYR plus GHRH (43.2 +/ - 6.0 ug/L; P < 0.05). Basal FFA levels were higher than those of norm al controls (P < 0.05). ACX (500 mg) decreased FFA levels in both obes e and normal subjects; the lowest FFA levels of obese subjects at 15 m in were similar to those of normal controls. ACX also potentiated GHRH -stimulated GH response in both obese and normal subjects. The GH resp onses potentiated by ACX in obesity (22.7 +/- 5.5 ug/L) were similar t o those of PYR plus GHRH in obese subjects and GHRH in normal controls , but they were lower than those of control treated with ACX plus GHRH (50.8 +/- 6.7 ug/L; P < 0.05). After the combined pretreatment with A CX and PYR, GH responses in obesity (44.1 +/- 6.0 ug/L) were significa ntly higher than those in GHRH test, PYR plus GHRH, and ACX plus GHRH in obese subjects (P < 0.05), and they were similar to PYR plus GHRH o r ACX plus GHRH in normal controls. However their enhanced GH response s were reduced compared with the control with ACX plus PYR plus GHRH ( 64.9 +/- 4.5 ug/L; P < 0.05). Our results are in agreement with the hy pothalamic hypothesis: an increase in somatostatinergic tone is respon sible for the blunted GH response to GHRH in obesity. In addition, the demonstration that the decreased FFA levels induced by ACX potentiate the somatotrope high plasma FFA levels play an important role in GH r esponsiveness in obesity, although other factors might also be involve d in GH derangements.