Effects of acipimox, an antilipolytic drug, on the growth hormone (GH) response to GH-releasing hormone alone or combined with arginine in obesity

Increased free fatty acid (FFA) levels of obese patients are likely involved in the pathogenesis of the growth hormone (GH) hyposecretion of obesity. To clarify their role, we studied the influence of inhibition of plasma FFA levels, induced by 500 mg oral acipimox (ACX), an antilipolytic drug, on the GH response to GH-releasing hormone (GHRH) alone or combined with arginine ([ARG] study A) in six normal women ([NS] aged 24 to 37 years; body mass index, 22.4 ± 0.9 kg/m 2) and six obese women ([OB] aged 21 to 40 years; body mass index, 39.5 ± 3.2 kg/m 2). In a group of seven OB patients (aged 18 to 58 years; body mass index, 35.8 ± 1.3 kg/m 2), the effect of ACX on either the GHRH- or GHRH+ARG-stimulated GH increase was also studied after a 4-day treatment with the same drug at 250 mg three times daily (study B). OB patients had baseline FFA levels higher than NS (0.77 ± 0.06 v 0.44 ± 0.09 mol/L, P < .05). In study A, ACX reduced FFA levels to the same nadir in both groups (0.11 ± 0.02 and 0.12 ± 0.03 mmol/L, NS and OB subjects, respectively). In NS, ACX failed to significantly potentiate the GH response to either GHRH (1,371.9 ± 425.2 v 1,001.8 ± 229.0 μg/L · min) or GHRH+ARG (3,558.4 ± 1,513.7 v 3,045.9 ± 441.8 μg/L · min), while in OB patients it increased the GH response to GHRH (797.6 ± 277.3 v 353.8 ± 136.7 μg/L · min, P < .01) and did not modify the response to ARG+GHRH (1,010.5 ± 253.1 v 821.1 ± 222.0 μg/L · min). In study B, ACX reduced FFA levels in OB patients (nadir, 0.09 ± 0.04 mmol/L). This treatment strikingly increased the GH response to GHRH (1,734.0 ± 725.4 v 271.5 ± 112.8 μg/L · min, P < .01) and significantly potentiated that to ARG+GHRH (2,371.9 ± 571.3 v 1,020.0 ± 343.2 μg/L · min, P < .05). In conclusion, our present findings indicate that an acute reduction of plasma FFA levels in OB patients restores their somatotrope responsiveness, whereas it does not affect GH secretion in lean subjects. After prolonged treatment, ACX further improves GHRH-stimulated GH secretion in OB patients, suggesting that elevated FFA levels play a leading role in the GH hyposecretory state of obesity.