Intermittent intraperitoneal infusion of peptide YY(3-36) reduces daily food intake and adiposity in obese rats.
Intermittent intraperitoneal infusion of peptide YY(3-36) reduces daily food intake and adiposity in obese rats.
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DOI：
10.1152/ajpregu.00164.2007
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发表时间：
2007-07
期刊：
影响因子：
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通讯作者：
P. Chelikani;A. Haver;R. Reidelberger
中科院分区：
文献类型：
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作者：
P. Chelikani;A. Haver;R. Reidelberger
多肽YY(3-36)[PYY(3-36)]是一种肠脑多肽，通过静脉输注给瘦小和肥胖的人和大鼠时，可以减少食物的摄入量。然而，通过渗透性小型泵长期给瘦鼠和肥胖的啮齿动物注射PYY(3-36)，只会导致每日摄食量和体重增加的一过性减少。最近有研究表明，连续10天每隔一小时静脉注射1小时的PYY(3-36)可持续减少瘦大鼠的每日摄食量、体重和肥胖。在这里，我们确定间歇服用PYY(3-36)是否可以在饮食诱导的肥胖大鼠中产生类似的反应。在21天的时间里，肥胖大鼠(体脂和GT；25%)在黑暗时期的1-3小时和7-9小时内每天接受两次Vehicle(n=18)或PYY(3-36)(n=24)的腹膜内注射。大鼠可以自由进食45%脂肪的固体饮食和29%的脂肪液体饮食；摄入量是通过连续记录食物容器重量的变化来确定的。为了维持每日卡路里摄入量减少15%-25%，初始剂量为30pmol.kg(-1).min(-1)的PYY(3-36)在第10天减少到10pmol.kg(-1).min(-1)，然后在第13天增加到17pmol.kg(-1).min(-1)。这种剂量策略使每日热量摄入量持续减少11-32%，并防止体重增加(8+/-6vs.51+/-11g)和脂肪沉积(4.4+/-7.6vs.41.0+/-12.8g)。这些结果表明，间歇性腹腔注射PYY(3-36)可以持续减少饮食诱导的肥胖啮齿动物的摄食量和肥胖，这些啮齿动物食用可口的高脂肪食物。
Peptide YY(3-36) [PYY(3-36)] is a gut-brain peptide that decreases food intake when administered by intravenous infusion to lean and obese humans and rats. However, chronic administration of PYY(3-36) by osmotic minipump to lean and obese rodents produces only a transient reduction in daily food intake and weight gain. It has recently been shown that 1-h intravenous infusions of PYY(3-36) every other hour for 10 days produced a sustained reduction in daily food intake, body weight, and adiposity in lean rats. Here, we determined whether intermittent delivery of PYY(3-36) can produce a similar response in diet-induced obese rats. During a 21-day period, obese rats (body fat >25%) received twice daily intraperitoneal infusion of vehicle (n = 18) or PYY(3-36) (n = 24) during hours 1-3 and 7-9 of the dark period. Rats had free access to both a 45% fat solid diet and a 29% fat liquid diet; intakes were determined from continuous computer recording of changes in food container weights. To sustain a 15-25% reduction in daily caloric intake, the initial PYY(3-36) dose of 30 pmol.kg(-1).min(-1) was reduced to 10 pmol.kg(-1).min(-1) on day 10 and then increased to 17 pmol.kg(-1).min(-1) on day 13. This dosing strategy produced a sustained reduction in daily caloric intake of 11-32% and prevented body weight gain (8 +/- 6 vs. 51 +/- 11 g) and fat deposition (4.4 +/- 7.6 vs. 41.0 +/- 12.8 g). These results indicate that intermittent intraperitoneal infusion of PYY(3-36) can produce a sustained reduction in food intake and adiposity in diet-induced obese rodents consuming palatable high-fat foods.