Attenuated peptide YY release in obese subjects is associated with reduced satiety
Attenuated peptide YY release in obese subjects is associated with reduced satiety
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DOI：
10.1210/en.2005-0972
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发表时间：
2006-01-01
期刊：
影响因子：
4.8
通讯作者：
Bloom, SR
中科院分区：
文献类型：
--
作者：
le Roux, CW;Batterham, RL;Bloom, SR
研究了20名正常体重和20名肥胖者对6种不同卡路里含量的试验餐的胃肠激素多肽YY(PYY)对食物的反应。在增加热量膳食的过程中，志愿者的血浆PYY水平逐渐升高(R-2=0.96P<；0.001)，但肥胖者在每种膳食规模下的内源性PYY反应都较低(P<；0.05在所有水平)。正常体重者和肥胖者血浆PYY1-36/PYY3-36比值相似。在12名志愿者中，还评估了分级剂量的外源性PYY3-36对食物摄入量和饱足感的影响。在人类中逐步增加外源性PYY3-36的剂量会导致食物摄入量的逐步减少(R-2=0.38；P<；0.001)。在高脂喂养的肥胖小鼠和保持正常体重的低脂喂养小鼠中，我们测量了血浆PYY、组织PYY和PYY mRNA水平，并评估了外源性PYY3-36对HF小鼠摄食量的影响。HF小鼠对外源性ip PYY3-36的厌食作用仍然敏感。与低脂喂养的小鼠相比，HF小鼠的内源性血浆PYY水平较低，组织PYY水平较高，但PYY mRNA水平相似，提示可能减少了PYY的释放。因此，肥胖人群和啮齿动物的空腹和餐后内源性血浆PYY水平降低。PYY3-36输注研究表明，肥胖者血浆PYY降低的程度可能与饱腹感降低和相对增加的食物摄入量有关。我们的结论是，肥胖的受试者有PYY缺乏，这会减少饱腹感，从而可能加剧他们的肥胖。
The responses of the gut hormone peptide YY ( PYY) to food were investigated in 20 normal-weight and 20 obese humans in response to six test meals of varying calorie content. Human volunteers had a graded rise in plasma PYY (R-2 = 0.96; P < 0.001) during increasing calorific meals, but the obese subjects had a lower endogenous PYY response at each meal size (P < 0.05 at all levels). The ratio of plasma PYY1-36 to PYY3-36 was similar in normal-weight and obese subjects. The effect on food intake and satiety of graded doses of exogenous PYY3-36 was also evaluated in 12 human volunteers. Stepwise increasing doses of exogenous PYY3-36 in humans caused a graded reduction in food intake (R-2 = 0.38; P < 0.001). In high-fat-fed (HF) mice that became obese and low-fat-fed mice that remained normal weight, we measured plasma PYY, tissue PYY, and PYY mRNA levels and assessed the effect of exogenous administered PYY3-36 on food intake in HF mice. HF mice remained sensitive to the anorectic effects of exogenous ip PYY3-36. Compared with low-fat-fed fed mice, the HF mice had lower endogenous plasma PYY and higher tissue PYY but similar PYY mRNA levels, suggesting a possible reduction of PYY release. Thus, fasting and postprandial endogenous plasma PYY levels were attenuated in obese humans and rodents. The PYY3-36 infusion study showed that the degree of plasma PYY reduction in obese subjects were likely associated with decreased satiety and relatively increased food intake. We conclude that obese subjects have a PYY deficiency that would reduce satiety and could thus reinforce their obesity.