抗脂解药物阿西莫司对肥胖患者单独使用生长激素释放激素或联合精氨酸时生长激素（GH）反应的影响。

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

作者信息

Maccario M, Procopio M, Grottoli S, Oleandri S E, Boffano G M, Taliano M, Camanni F, Ghigo E

机构信息

Department of Clinical Pathophysiology, University of Turin, Italy.

出版信息

Metabolism. 1996 Mar;45(3):342-6. doi: 10.1016/s0026-0495(96)90288-7.

DOI:10.1016/s0026-0495(96)90288-7

PMID:8606641

Abstract

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/m2) and six obese women ([OB] aged 21 to 40 years; body mass index 39.5 +/- 3.2 kg/m2). In a group of seven OB patients (aged 18 to 58 years; body mass index, 35.8 +/- 1.3 kg/m2), the effect of ACX on either 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 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 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 micrograms/L x min) or GHRH+ARG (3558.4 +/- 1,513.7 v 3,045.9 +/- 441.8 micrograms/L x min), while in OB patients it increased the GH response to GHRH (797.6 +/- 277.3 v 353.8 +/- 136.7 micrograms/L x min, P<.01) and did not modify the response to ARG+GHRH (1,010.5 +/- 253.1 v 821.1 +/- 222.0 micrograms/L x 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 micrograms/L x min, P<.01) and significantly potentiated that to ARG+GHRH (2,371.9 +/- 571.3 v 1,020.0 +/- 343.2 micrograms/L x 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.

摘要

肥胖患者游离脂肪酸（FFA）水平升高可能参与肥胖患者生长激素（GH）分泌不足的发病机制。为阐明其作用，我们研究了口服500 mg抗脂解药物阿西莫司（ACX）诱导的血浆FFA水平抑制对6名正常女性（[NS]，年龄24至37岁；体重指数，22.4±0.9 kg/m²）和6名肥胖女性（[OB]，年龄21至40岁；体重指数39.5±3.2 kg/m²）单独使用生长激素释放激素（GHRH）或联合精氨酸时GH反应的影响（[ARG]研究A）。在一组7名OB患者（年龄18至58岁；体重指数，35.8±1.3 kg/m²）中，在每天3次服用250 mg相同药物进行4天治疗后，还研究了ACX对GHRH或GHRH + ARG刺激的GH升高的影响（研究B）。OB患者基线FFA水平高于NS（0.77±0.06对0.44±0.09 mmol/L，P<0.05）。在研究A中，ACX使两组FFA水平降至相同最低点（分别为0.11±0.02和0.12±0.03 mmol/L，NS和OB受试者）。在NS中，ACX未能显著增强对GHRH（1,371.9±425.2对1,001.8±229.0微克/L·分钟）或GHRH + ARG（3558.4±1,513.7对3,045.9±441.8微克/L·分钟）的GH反应，而在OB患者中，它增加了对GHRH的GH反应（797.6±277.3对353.8±136.7微克/L·分钟，P<0.01），并且未改变对ARG + GHRH的反应（1,010.5±253.1对821.1±222.0微克/L·分钟）。在研究B中，ACX降低了OB患者的FFA水平（最低点，0.09±0.04 mmol/L）。这种治疗显著增加了对GHRH的GH反应（1,734.0±72,5.4对271.5±112.8微克/L·分钟，P<0.01），并显著增强了对ARG + GHRH的反应（2,371.9±571.3对1,020.0±343.2微克/L·分钟，P<0.05）。总之，我们目前的研究结果表明，OB患者血浆FFA水平的急性降低恢复了其生长激素细胞反应性，而对瘦人受试者的GH分泌没有影响。经过长期治疗，ACX进一步改善了OB患者GHRH刺激的GH分泌，表明升高的FFA水平在肥胖患者GH分泌不足状态中起主导作用。