Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome
Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome
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DOI：
10.1210/jc.2002-021052
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发表时间：
2003-01-01
影响因子：
5.8
通讯作者：
Purnell, JQ
中科院分区：
文献类型：
--
作者：
Haqq, AM;Farooqi, IS;Purnell, JQ
Ghrelin是GH促分泌素受体的内源性配体，当以药理学剂量给予时，在动物模型和人类中刺激食欲并导致肥胖。Prader-Willi综合征（PWS）是一种遗传性肥胖综合征，其特征是生长激素缺乏和儿童期食欲旺盛和肥胖。因此，我们假设生长激素释放肽水平可能在这种综合征中肥胖的表达中发挥作用。我们测量了13名PWS儿童的空腹血清ghrelin水平，他们的平均年龄为9.5岁（范围，5-15岁），体重指数（BMI）为31.3 kg/m2（范围，22-46）。PWS组与4个对照组进行比较：20名年龄和性别匹配的正常体重对照组，17名肥胖儿童（00），14名年龄，性别和BMI匹配的黑皮质素-4受体突变（MC 4）儿童，以及3名瘦素缺乏症儿童（013）。在非PWS受试者中，ghrelin水平与年龄（r = 0.36，P = 0.007）、胰岛素（r = 0.55，P < 0.001）和BMI（r = 0.62，P < 0.001）呈负相关，但与瘦素无关。在PWS儿童中，空腹ghrelin浓度与正常体重对照组相比无显著差异（平均值+/-（SD）; 429 +/- 374 vs. 270 +/- 102 pmol/L; P = 0.14）。然而，与所有肥胖组相比，PWS儿童确实表现出更高的空腹ghrelin浓度（3- 4倍升高）（OC，MC 4，013）（平均值+/- SD; 429：L 374 vs. 139 +/- 70 pmol/L; P < 0.001）。总之，与BMI匹配的肥胖对照组（OC，MC 4，OB）相比，PWS儿童的ghrelin水平显著升高（3至4倍）。血清生长激素释放肽水平升高到本研究中记录的程度可能作为一种促食欲因素发挥作用，驱动PWS中发现的贪得无厌的食欲和肥胖。
Ghrelin, an endogenous ligand of the GH secretagogue receptor, stimulates appetite and causes obesity in animal models and in humans when given in pharmacologic doses. Prader-Willi Syndrome (PWS) is a genetic obesity syndrome characterized by GH deficiency and the onset of a voracious appetite and obesity in childhood. We, therefore, hypothesized that ghrelin levels may play a role in the expression of obesity in this syndrome. We measured fasting serum ghrelin levels in 13 PWS children with an average age of 9.5 yr (range, 5-15) and body mass index (BMI) of 31.3 kg/m(2) (range, 22-46). The PWS group was compared with 4 control groups: 20 normal weight controls matched for age and sex, 17 obese children (00, and 14 children with melanocortin-4 receptor mutations (MC4) matched for age, sex, and BMI, and a group of 3 children with leptin deficiency (013). In non-PWS subjects, ghrelin levels were inversely correlated with age (r = 0.36, P = 0.007), insulin (r = 0.55, P < 0.001), and BMI (r = 0.62, P < 0.001), but not leptin. In children with PWS, fasting ghrelin concentrations were not significantly different compared with normal weight controls (mean +/- (SD); 429 +/- 374 vs. 270 +/- 102 pmol/liter; P = 0.14). However, children with PWS did demonstrate higher fasting ghrelin concentrations (3- to 4-fold elevation) compared with all obese groups (OC, MC4, 013) (mean +/- SD; 429 :L 374 vs. 139 +/- 70 pmol/liter; P < 0.001). In conclusion, ghrelin levels in children with PWS are significantly elevated (3- to 4-fold) compared with BMI-matched obese controls (OC, MC4, OB). Elevation of serum ghrelin levels to the degree documented in this study may play a role as an orexigenic factor driving the insatiable appetite and obesity found in PWS.