A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.
A peptidomimetic targeting white fat causes weight loss and improved insulin resistance in obese monkeys.
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DOI：
10.1126/scitranslmed.3002621
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发表时间：
2011-11-09
影响因子：
17.1
通讯作者：
Pasqualini R
中科院分区：
文献类型：
--
作者：
Barnhart KF;Christianson DR;Hanley PW;Driessen WH;Bernacky BJ;Baze WB;Wen S;Tian M;Ma J;Kolonin MG;Saha PK;Do KA;Hulvat JF;Gelovani JG;Chan L;Arap W;Pasqualini R
肥胖被定义为身体质量指数大于30，是全球发病率和死亡率的主要原因，也是一种经济负担。尽管在过去的十年中做出了巨大的努力，但很少有药物能够成功地用于治疗肥胖患者。啮齿动物和灵长类动物之间的生物学差异是将在啮齿动物身上发现或开发的抗肥胖策略转化为有效的人类治疗方法的主要障碍。在这里，我们在肥胖的旧大陆猴子中评估了配体导向的拟肽CKGGRAKDC-GG-D(KLAKLAK)2（以后称为脂肪肽）。脂肪肽治疗可诱导白色脂肪组织血管内的靶向凋亡，导致肥胖猴子体重迅速减轻并改善胰岛素抵抗。磁共振成像和双能x线吸收仪证实白色脂肪组织明显减少。在实验确定的最佳剂量下，来自三个不同物种的猴子在肾近端小管功能上表现出可预测和可逆的变化。总之，灵长类动物的这些数据确立了脂肪肽作为一类新的候选药物的原型，可能对治疗人类肥胖有用。
Obesity, defined as body mass index greater than 30, is a leading cause of morbidity and mortality and a financial burden worldwide. Despite significant efforts in the past decade, very few drugs have been successfully developed for the treatment of obese patients. Biological differences between rodents and primates are a major hurdle for translation of anti-obesity strategies either discovered or developed in rodents into effective human therapeutics. Here, we evaluate the ligand-directed peptidomimetic CKGGRAKDC-GG-D(KLAKLAK)2 (henceforth termed adipotide) in obese Old World monkeys. Treatment with adipotide induced targeted apoptosis within blood vessels of white adipose tissue and resulted in rapid weight loss and improved insulin resistance in obese monkeys. Magnetic resonance imaging and dual-energy x-ray absorptiometry confirmed a marked reduction in white adipose tissue. At experimentally determined optimal doses, monkeys from three different species displayed predictable and reversible changes in renal proximal tubule function. Together, these data in primates establish adipotide as a prototype in a new class of candidate drugs that may be useful for treating obesity in humans.
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DOI：
10.1093/gerona/60.12.1518
发表时间：
2005-12-01
影响因子：
5.1
作者：
Raman, A;Colman, RJ;Schoeller, DA
通讯作者：
Schoeller, DA
DOI：
10.1016/1071-5576(95)00023-8
发表时间：
1995-09-01
期刊：
JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION
影响因子：
--
作者：
DIAMOND, MP;THORNTON, K;DEFRONZO, RA
通讯作者：
DEFRONZO, RA
影响因子：
82.9
作者：
Kolonin, MG;Saha, PK;Arap, W
通讯作者：
Arap, W
DOI：
10.1152/ajprenal.00441.2006
发表时间：
2007-07-01
影响因子：
4.2
作者：
Krug, Alexander W.;Voelker, Katharina;Silbernagl, Stefan
通讯作者：
Silbernagl, Stefan
DOI：
10.1074/jbc.m804595200
发表时间：
2008-10-24
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Giordano RJ;Lahdenranta J;Zhen L;Chukwueke U;Petrache I;Langley RR;Fidler IJ;Pasqualini R;Tuder RM;Arap W
通讯作者：
Arap W