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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice
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A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice

机译：神经肽Y Y5拮抗剂可选择性改善饮食诱发的肥胖小鼠的体重增加和相关参数

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摘要

Neuropeptide Y (NPY) is thought to have a major role in the physiological control of energy homeostasis. Among five NPY receptors described, the NPY Y5 receptor (Y5R) is a prime candidate to mediate some of the effects of NPY on energy homeostasis, although its role in physiologically relevant rodent obesity models remains poorly defined. We examined the effect of a potent and highly selective Y5R antagonist in rodent obesity and dietary models. The Y5R antagonist selectively ameliorated diet-induced obesity (DIO) in rodents by suppressing body weight gain and adiposity while improving the DIO-associated hyperinsulinemia. The compound did not affect the body weight of lean mice fed a regular diet or genetically obese leptin receptor-deficient mice or rats, despite similarly high brain Y5R receptor occupancy. The Y5R antagonist acts in a mechanism-based manner, as the compound did not affect DIO of Y5R-deficient mice. These results indicate that Y5R is involved in the regulation and development of DIO and suggest utility for Y5R antagonists in the treatment of obesity.
机译：人们认为神经肽Y（NPY）在能量稳态的生理控制中起主要作用。在描述的五种NPY受体中，NPY Y5受体（Y5R）是介导NPY对能量稳态的某些影响的主要候选者，尽管在生理相关的啮齿类肥胖症模型中的作用仍不清楚。我们在啮齿类肥胖症和饮食模型中研究了一种有效且高度选择性的Y5R拮抗剂的作用。 Y5R拮抗剂通过抑制体重增加和肥胖，同时改善与DIO相关的高胰岛素血症，选择性地改善了啮齿动物的饮食诱导型肥胖（DIO）。尽管具有相似的大脑Y5R受体高占用率，但该化合物不会影响进食常规饮食的瘦小鼠或遗传性瘦素受体缺陷型小鼠或大鼠的体重。 Y5R拮抗剂以基于机制的方式起作用，因为该化合物不影响Y5R缺陷小鼠的DIO。这些结果表明Y5R参与DIO的调节和发育，并提示Y5R拮抗剂可用于治疗肥胖症。

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