Diabetes & Obesity Research Program, Garvan Institute of Medical Research, Sydney-Darlinghurst, Australia.
Neuropeptides. 2011 Aug;45(4):301-7. doi: 10.1016/j.npep.2011.06.001. Epub 2011 Jul 1.
Prader-Willi syndrome (PWS) is a leading genetic cause of obesity, characterized by hyperphagia, endocrine and developmental disorders. It is suggested that the intense hyperphagia could stem, in part, from impaired gut hormone signaling. Previous studies produced conflicting results, being confounded by differences in body composition between PWS and control subjects.
Fasting and postprandial gut hormone responses were investigated in a cross-sectional cohort study including 10 adult PWS, 12 obese subjects matched for percentage body fat and central abdominal fat, and 10 healthy normal weight subjects.
PYY[total], PYY[3-36], GLP-1[active] and ghrelin[total] were measured by ELISA or radioimmunoassay. Body composition was assessed by dual energy X-ray absorptiometry. Visual analog scales were used to assess hunger and satiety.
In contrast to lean subjects (p<0.05), PWS and obese subjects were similarly insulin resistant and had similar insulin levels. Ghrelin[total] levels were significantly higher in PWS compared to obese subjects before and during the meal (p<0.05). PYY[3-36] meal responses were higher in PWS than in lean subjects (p=0.01), but not significantly different to obese (p=0.08), with an additional non-significant trend in PYY[total] levels. There were no significant differences in self-reported satiety between groups, however PWS subjects reported more hunger throughout (p=0.003), and exhibited a markedly reduced meal-induced suppression of hunger (p=0.01) compared to lean or obese subjects.
Compared to adiposity-matched control subjects, hyperphagia in PWS is not related to a lower postprandial GLP-1 or PYY response. Elevated ghrelin levels in PWS are consistent with increased hunger and are unrelated to insulin levels.
普拉德-威利综合征（PWS）是肥胖的主要遗传原因，其特征为食欲过盛、内分泌和发育障碍。有研究表明，强烈的食欲过盛可能部分源于肠道激素信号受损。先前的研究结果相互矛盾，这是由于 PWS 患者和对照组之间的身体成分存在差异而导致结果混淆。
本横断面研究纳入了 10 名成年 PWS 患者、12 名体脂百分比和中央腹部脂肪与 PWS 患者相匹配的肥胖受试者，以及 10 名健康的正常体重受试者，对其进行了禁食和餐后肠道激素反应的研究。
采用 ELISA 或放射免疫法检测 PYY[总]、PYY[3-36]、GLP-1[活性]和 ghrelin[总]。采用双能 X 射线吸收法评估身体成分。使用视觉模拟评分法评估饥饿感和饱腹感。
与瘦受试者相比（p<0.05），PWS 患者和肥胖受试者的胰岛素抵抗情况相似，胰岛素水平也相似。与肥胖受试者相比，PWS 患者的 ghrelin[总]水平在餐前和餐中均显著升高（p<0.05）。与瘦受试者相比，PWS 患者的 PYY[3-36]餐后反应更高（p=0.01），但与肥胖受试者相比无显著差异（p=0.08），PYY[总]水平也有进一步的非显著趋势。各组间的自我报告饱腹感无显著差异，但 PWS 患者始终报告饥饿感更强（p=0.003），且其餐后饥饿感抑制程度明显降低（p=0.01），与瘦或肥胖受试者相比均有显著差异。
与体脂匹配的对照组相比，PWS 患者的食欲过盛与餐后 GLP-1 或 PYY 反应降低无关。PWS 患者中升高的 ghrelin 水平与食欲增加一致，与胰岛素水平无关。
