Tagliaferri M, Scacchi M, Pincelli A I, Berselli M E, Silvestri P, Montesano A, Ortolani S, Dubini A, Cavagnini F
IRCCS Ospedale San Giuseppe, Istituto Auxologico Italiano, Piancavallo (Verbania).
Int J Obes Relat Metab Disord. 1998 Sep;22(9):836-41. doi: 10.1038/sj.ijo.0800669.
Severe energy restriction in the treatment of obesity is limited by catabolism of body protein stores and, consequently, loss of lean as well as fat tissue. Growth hormone (GH), whose secretion is markedly impaired in obesity, is endowed with both lipolytic and protein anabolic properties. The aim of this study was to verify the effects of GH administration on body composition, plasma leptin levels and energy metabolism in obese patients undergoing severe dietary restriction.
Single-blind placebo-controlled study. Twenty obese women were fed a diet of 41.86 kJ/kg ideal body weight (IBW) daily for 4 weeks: 10 of them were randomly assigned to a 4 week treatment with biosynthetic GH (rhGH, Saizen, Serono, Rome, Italy), 1 U/kg IBW/week in daily subcutaneous injections; the other 10 patients, matched for age and BMI, received vehicle only.
Twenty women with simple obesity (age: 25.4+/-1.07 y, BMI: 35.9+/-0.35 kg/m2).
Plasma IGF-I and leptin, serum markers of bone turnover (serum bone isoenzyme of alkaline phosphatase, osteocalcin and urinary hydroxyproline), nitrogen balance, body composition (by DEXA), and resting energy expenditure (REE, by indirect calorimetry) were evaluated at baseline and after 4 weeks.
Mean IGF-I plasma levels, not influenced by energy restriction in patients receiving placebo, displayed a significant increase in the group treated with rhGH. The mean weight reduction and fat mass loss were not significantly different in the two groups (6.0+/-0.51 vs 7.2+/-0.30 kg, NS, and 5.36+/-0.460 vs 4.28+/-0.572 kg, NS, with rhGH and placebo, respectively). Likewise, plasma leptin levels decreased significantly in weight-reduced subjects receiving either rhGH (from 16.2+/-2.37 to 6.4+/-0.39 ng/ml, P < 0.05) or placebo (from 14.3+/-2.55 to 7.7+/-3.77 ng/ml, P < 0.05). On the contrary, the mean decrease of lean body mass (LBM) was significantly lower in the GH-treated patients than in those receiving vehicle (1.52+/-0.60 vs 3.79+/-0.45 kg, P < 0.05). In keeping with these findings, the mean daily nitrogen balance was significantly less negative in the GH-treated subjects than in the vehicle-injected patients (mean of the 4 week daily urine collections -185.7+/-40.33 vs -363.9+/-55.47 mmol/d, P < 0.05, respectively). Further, a significant reduction of mean REE was recorded in the energy-restricted placebo-treated patients (from 8807+/-498 to 7580+/-321 kJ/24 h, P < 0.05), but not in the patients receiving rhGH (from 8367+/-580 to 8903+/-478 kJ/24 h, NS). Actually, when corrected for LBM, REE was even increased by GH administration (from 197.9+/-11.76 to 219.3+/-9.87 kJ/kg LBM/24 h, P < 0.05), whereas it was unchanged in the placebo group (from 201.7+/-13.85 to 190.0+/-9.87 kJ/kg LBM/24 h, NS). A tendency of serum markers of bone turnover to increase was observed in the patients treated with rhGH, however with no changes in bone mineral content and density.
rhGH treatment, though unable to enhance diet-induced weight and fat mass reduction, was effective in stimulating IGF-I production and conserving LBM and increasing its energy metabolism even in the presence of severe energy restriction.
肥胖治疗中严格的能量限制受机体蛋白质储备分解代谢的限制，进而导致瘦组织和脂肪组织均减少。生长激素（GH）在肥胖患者中分泌显著受损，它具有脂解和蛋白质合成代谢特性。本研究旨在验证给予GH对接受严格饮食限制的肥胖患者身体成分、血浆瘦素水平及能量代谢的影响。
单盲安慰剂对照研究。20名肥胖女性每日按41.86 kJ/kg理想体重（IBW）进食，持续4周：其中10名被随机分配接受为期4周的生物合成GH（重组人生长激素，思增，雪兰诺公司，罗马，意大利）治疗，每周1 U/kg IBW，每日皮下注射；另外10名年龄和BMI相匹配的患者仅接受赋形剂。
20名单纯性肥胖女性（年龄：25.4±1.07岁，BMI：35.9±0.35 kg/m²）。
在基线及4周后评估血浆IGF-I和瘦素、骨转换血清标志物（血清骨碱性磷酸酶同工酶、骨钙素和尿羟脯氨酸）、氮平衡、身体成分（通过双能X线吸收法）以及静息能量消耗（REE，通过间接测热法）。
接受安慰剂的患者中，血浆IGF-I平均水平不受能量限制影响，而接受重组人生长激素治疗的组中该水平显著升高。两组的平均体重减轻和脂肪量减少无显著差异（重组人生长激素组和安慰剂组分别为6.0±0.51 vs 7.2±0.30 kg，无统计学意义；5.36±0.460 vs 4.28±0.572 kg，无统计学意义）。同样，接受重组人生长激素（从16.2±2.37降至6.4±0.39 ng/ml，P<0.05）或安慰剂（从14.3±2.55降至7.7±3.77 ng/ml，P<0.05）治疗且体重减轻的受试者血浆瘦素水平均显著降低。相反，接受生长激素治疗的患者瘦体重（LBM）平均减少量显著低于接受赋形剂的患者（1.52±0.60 vs 3.79±0.45 kg，P<0.05）。与这些结果一致，接受生长激素治疗的受试者平均每日氮平衡显著低于接受赋形剂注射的患者（4周每日尿收集量平均值分别为-185.7±40.33 vs -363.9±55.47 mmol/d，P<0.05）。此外，接受能量限制的安慰剂治疗患者的平均REE显著降低（从8807±498降至7580±321 kJ/24 h，P<0.05），而接受重组人生长激素治疗的患者则未降低（从8367±580升至8903±478 kJ/24 h，无统计学意义）。实际上，校正LBM后，生长激素给药使REE升高（从197.9±11.76升至219.3±9.87 kJ/kg LBM/24 h，P<0.05），而安慰剂组则无变化（从201.7±13.85降至190.0±9.87 kJ/kg LBM/24 h，无统计学意义）。接受重组人生长激素治疗的患者骨转换血清标志物有升高趋势，但骨矿物质含量和密度无变化。
重组人生长激素治疗虽不能增强饮食诱导的体重和脂肪量减少，但即使在严格能量限制情况下，仍能有效刺激IGF-I生成，保留瘦体重并增加其能量代谢。
