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 in volved in the pathogenesis of the growth hormone (GH) hyposecretion of obesity. To clarify their role, we studied the influence of inhibitio n of plasma FFA levels, induced by 500 mg oral acipimox (ACX), an anti lipolytic drug, on the GH response to GH-releasing hormone (GHRH) alon e 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 ob ese women ([OB] aged 27 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- o r GHRH+ARG-stimulated GH increase was also studied after a 4-day treat ment with the same drug at 250 mg three times daily (study B). OB pati ents had baseline FFA levels higher than NS (0.77 +/- 0.06 v 0.44 +/- 0.09 mmol/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 O B subjects, respectively). In NS, ACX failed to significantly potentia te the GH response to either GHRH (1,371.9 +/- 425.2 v 1,001.8 +/- 229 .0 mu g/L . min) or GHRH+ARG (3,558.4 +/- 1,513.7 v 3,045.9 +/- 441.8 mu g/L . min), while in OB patients it increased the GH response to GH RH (797.6 +/- 277.3 v 353.8 +/- 136.7 mu g/L . min, P < .01) and did n ot modify the response to ARG+GHRH (1,010.5 +/- 253.1 v 821.1 +/- 222. 0 mu g/L . min). In study B, ACX reduced FFA levels in OB patients (na dir, 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 mu g/L . min, P < .01) and significantly potentiated that to ARG+GHRH (2,371.9 +/- 57 1.3 v 1,020.0 +/- 343.2 mu g/L . min, P < .05). In conclusion, our pre sent findings indicate that an acute reduction of plasma FFA levels in OB patients restores their somatotrope responsiveness, whereas it doe s not affect GH secretion in lean subjects. After prolonged treatment, ACX further improves GHRH-stimulated GH secretion in OB patients, sug gesting that elevated FFA levels play a leading role in the GH hyposec retory state of obesity. Copyright (C) 1996 by W.B. Saunders Company