Agouti-related protein-deficient mice display an age-related lean phenotype
Agouti-related protein-deficient mice display an age-related lean phenotype
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DOI：
10.1016/j.cmet.2005.11.004
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发表时间：
2005-12-01
期刊：
影响因子：
29
通讯作者：
Sleeman, MW
中科院分区：
文献类型：
--
作者：
Wortley, KE;Anderson, KD;Sleeman, MW
中枢黑皮质素系统的内源性调节剂，例如刺鼠相关蛋白（AgRP），应该在能量摄入和消耗的调节中占据关键地位。尽管如此，最近报道AgRP缺陷小鼠表现出正常的食物摄入，体重增加和能量消耗。在这里，我们证明了2至3个月大的Agrp基因敲除小鼠实际上表现出对喂养挑战（禁食和MCR激动剂）的微妙变化，但更重要和更大的是，在6个月大后表现出体重减轻和肥胖。这种年龄依赖性瘦表型与代谢率、体温和自发活动增加以及循环甲状腺激素（T4和T3）和BAT UCP-1表达增加相关。这些结果进一步证明了AgRP神经元系统在能量稳态调节中的重要性。
Endogenous modulators of the central melanocortin system, such as the agouti-related protein (AgRP), should hold a pivotal position in the regulation of energy intake and expenditure. Despite this, AgRP-deficient mice were recently reported to exhibit normal food intake, body weight gain, and energy expenditure. Here we demonstrate that 2- to 3-month-old Agrp null mice do in fact exhibit subtle changes in response to feeding challenges (fasting and MCR agonists) but, of more significance and magnitude, exhibit reduced body weight and adiposity after 6 months of age. This age-dependent lean phenotype is correlated with increased metabolic rate, body temperature, and locomotor activity and increased circulating thyroid hormone (T4 and T3) and BAT UCP-1 expression. These results provide further proof of the importance of the AgRP neuronal system in the regulation of energy homeostasis.