Rasmussen Michael H, Juul Anders, Hilsted Jannik
Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Denmark.
Obesity (Silver Spring). 2007 Apr;15(4):879-86. doi: 10.1038/oby.2007.607.
It has been hypothesized that increased free insulin-like growth factor (IGF)-I levels generated from an increase in IGF-binding protein (IGFBP) protease activity could be the inhibitory mechanism for the decreased growth hormone (GH) secretion observed in obese subjects.
In this study, we determined basal and 24-hour levels of free IGF-I and -II, total IGF-I and -II, IGFBP-1, as well as basal IGFBP-2, -3, and -4, acid-labile subunit (ALS), IGFBP-1, -2, and -3 protease activity, and 24-hour GH release in obese women before and after a diet-induced weight loss. Sixteen obese women (age, 29.5+/-1.4 years) participated in a weight loss program and 16 age-matched non-obese women served as controls.
Circulating free IGF-I and 24-hour GH release were significantly decreased in obese women at before weight loss compared with non-obese women (1.29+/-0.12 vs. 0.60+/-0.09 microg/L; p<0.001 and 862+/-90 vs. 404+/-77 mU/24 hours; p<0.001, respectively). Free IGF-I and 24-hour GH release were not inversely correlated to each other. IGFBP-1 and -2 levels were decreased, whereas ALS, IGFBP-3 and -4, and IGFBP-1, -2, and -3 protease activity were similar in obese and non-obese women. Eight of the 16 obese women achieved an average weight loss of 30+/-5 kg during 26 to 60 weeks of dieting. After the considerable weight loss, significant differences in free IGF-I, GH release, and IGFBP-1 and -2 levels were no longer present between previously obese and non-obese women.
We showed that circulating free IGF-I is markedly decreased in severely obese women and does not per se mediate the concomitant hyposomatotropism. The decreased levels of free IGF-I seem to be transient and restored to normal levels after weight loss.
有假说认为，胰岛素样生长因子结合蛋白（IGFBP）蛋白酶活性增加所产生的游离胰岛素样生长因子（IGF）-I水平升高，可能是肥胖受试者生长激素（GH）分泌减少的抑制机制。
在本研究中，我们测定了肥胖女性在饮食诱导体重减轻前后游离IGF-I和-II、总IGF-I和-II、IGFBP-1以及基础IGFBP-2、-3和-4、酸不稳定亚基（ALS）、IGFBP-1、-2和-3蛋白酶活性以及24小时GH释放的基础水平和24小时水平。16名肥胖女性（年龄29.5±1.4岁）参加了减肥计划，16名年龄匹配的非肥胖女性作为对照。
与非肥胖女性相比，肥胖女性体重减轻前循环游离IGF-I和24小时GH释放显著降低（分别为1.29±0.12 vs. 0.60±0.09 μg/L；p<0.001和862±90 vs. 404±77 mU/24小时；p<0.001）。游离IGF-I和24小时GH释放彼此不呈负相关。肥胖和非肥胖女性的IGFBP-1和-2水平降低，而ALS、IGFBP-3和-4以及IGFBP-1、-2和-3蛋白酶活性相似。16名肥胖女性中有8名在26至60周的节食期间平均体重减轻了30±5 kg。在显著体重减轻后，先前肥胖和非肥胖女性之间游离IGF-I、GH释放以及IGFBP-1和-2水平不再存在显著差异。
我们表明，严重肥胖女性循环游离IGF-I显著降低，且其本身并不介导伴随的生长激素分泌不足。游离IGF-I水平降低似乎是暂时的，体重减轻后恢复到正常水平。
