Chronic administration of OB protein decreases food intake by selectively reducing meal size in male rats

Chronic administration of OB protein decreases food intake by selectively reducing meal size in male rats
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DOI:
10.1152/ajpregu.1998.275.1.r180
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发表时间:
1998-07-01
影响因子:
2.8
通讯作者:
Langhans, W
Langhans, W
中科院分区:
医学3区
文献类型:
--
作者:
Kahler, A;Geary, N;Langhans, W

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OB蛋白(OB)的强效自噬作用已被证实,但其作用机制在很大程度上尚不清楚。我们对24只成年雄性Sprague-Dawley大鼠(研究开始时体重:292 g)长期服用一种半衰期延长的新型改性重组人OB (Mod-OB)对其随意进食、自发进食模式和体重的影响进行了研究。从注射第3天到注射后第3天,连续8天皮下注射Mod-OB(每天4 mg/kg),与车辆注射相比,可显著减少随意食物摄入量。注射mod - ob的大鼠比对照组每天少吃4.5至7.1 g(或13-20%),这种减少主要发生在黑暗时期。从注射第8天到注射后第4天,对Mod-OB的反应显著降低了体重增加,注射后第3天最大差异为24 g。Mod-OB减少食物摄入量的主要原因是夜间自发食量减少21-34%。Mod-OB对夜间进食频率和持续时间无显著影响。Mod-OB也不可靠地影响一日三餐的大小、持续时间或频率。注射mod - ob后大鼠无代偿性贪食现象。这些结果表明,长期给药OB选择性地影响控制雄性大鼠膳食大小的机制。
The potent hypophagic effect of OB protein (OB) is well established, but the mechanism of this effect is largely unknown. We investigated the effects of chronic administration of a novel modified recombinant human OB (Mod-OB) with a prolonged half-life (>48 h) on ad libitum food intake, spontaneous meal patterns, and body weight in 24 adult, male Sprague-Dawley rats (body weight at study onset: 292 g). Single daily subcutaneous injections of Mod-OB (4 mg/kg daily) for 8 consecutive days significantly reduced ad libitum food intake compared with vehicle injections from injection day 3 through postinjection day 3. Mod-OB-injected rats ate between 4.5 and 7.1 g(or 13-20%) per day less than controls, with the reduction primarily occurring during the dark period. Body weight gain was significantly decreased in response to Mod-OB from injection day 8 until postinjection day 4, with a maximum difference of 24 g on postinjection day 3. The reduction of food intake by Mod-OB was mainly due to a 21-34% decrease in nocturnal spontaneous meal size. There was no significant effect of Mod-OB on nocturnal meal frequency or duration. Mod-OB also did not reliably affect the size, duration, or frequency of diurnal meals. Mod-OB-injected rats displayed no compensatory hyperphagia after the injection period. These results indicate that chronically administered OB selectively affects the mechanisms controlling meal size in male rats.