Hara Junko, Yanagisawa Masashi, Sakurai Takeshi
Institute of Basic Medical Sciences, Department of Pharmacology, University of Tsukuba, Ibaraki 305-8575, Japan.
Neurosci Lett. 2005 Jun 3;380(3):239-42. doi: 10.1016/j.neulet.2005.01.046. Epub 2005 Feb 8.
Orexins are a pair of neuropeptides expressed by a population of neurons located in the lateral hypothalamic area (LHA). Prepro-orexin- or orexin receptor type 2-deficient animals exhibit a phenotype remarkably similar to the human sleep disorder, narcolepsy, which is characterized by sleep/wakefulness fragmentation. Human narcolepsy is known to be associated with metabolic abnormalities, including an increased frequency of obesity and non-insulin-dependent diabetes mellitus. Complex disruption of energy homeostasis in orexin neuron-deficient transgenic mice (orexin/ataxin-3 mice) is also manifested as late-onset obesity despite eating less. Here, we report that the development of obesity in orexin neuron-ablated narcoleptic mice is critically dependent on their genetic background and environmental factors, and the phenotype is different from that of prepro-orexin knockout mice even under the same genetic background and environmental factors, suggesting that factors that co-localize in orexin neurons might have important roles in the regulation of energy homeostasis. Our observation also suggests that the obesity observed in orexin neuron-deficient narcolepsy is dependent on the genetic background and environmental factors.
食欲素是由位于下丘脑外侧区(LHA)的一群神经元表达的一对神经肽。前食欲素或2型食欲素受体缺陷的动物表现出一种与人类睡眠障碍发作性睡病非常相似的表型,其特征是睡眠/觉醒碎片化。已知人类发作性睡病与代谢异常有关,包括肥胖和非胰岛素依赖型糖尿病的发病率增加。尽管食欲素神经元缺陷的转基因小鼠(食欲素/ataxin-3小鼠)进食较少,但能量稳态的复杂破坏也表现为迟发性肥胖。在这里,我们报告说,食欲素神经元消融的发作性睡病小鼠肥胖的发生严重依赖于它们的遗传背景和环境因素,并且即使在相同的遗传背景和环境因素下,其表型也与前食欲素敲除小鼠不同,这表明与食欲素神经元共定位的因素可能在能量稳态调节中起重要作用。我们的观察还表明,在食欲素神经元缺陷的发作性睡病中观察到的肥胖依赖于遗传背景和环境因素。