Characterization of neuropeptide Y (NPY) Y5 receptor-mediated obesity in mice:: Chronic intracerebroventricular infusion of D-Trp34NPY
Characterization of neuropeptide Y (NPY) Y5 receptor-mediated obesity in mice:: Chronic intracerebroventricular infusion of D-Trp34NPY
复制标题
DOI：
10.1210/en.2002-0119
复制
发表时间：
2003-05-01
期刊：
影响因子：
4.8
通讯作者：
Kanatani, A
中科院分区：
文献类型：
--
作者：
Mashiko, S;Ishihara, A;Kanatani, A
为了阐明神经肽Y（NPY）Y 5受体亚型在能量稳态中的作用，在C57 BL/6 J小鼠中研究了脑室内输注选择性Y 5激动剂D-Trp（NPY）-N-34的作用。脑室内输注D-Trp（34）NPY（5和10 μ g/d）可引起食欲亢进和体重增加，并伴有脂肪组织重量增加、高胆固醇血症、高胰岛素血症和高瘦素血症。以100 mg/kg的剂量每天两次口服给予选择性Y 5拮抗剂完全抑制了所有这些D-Trp（34）NPY诱导的变化，表明Y 5受体的慢性激活产生食欲过盛和肥胖。此外，D-Trp（34）NPY仍导致脂肪组织重量增加，并伴有高瘦素血症和高胆固醇血症，尽管D-Trp（34）NPY诱导的食物摄入受到成对喂养的限制。在配对饲养条件下，D-Trp（34）NPY可降低白色脂肪组织中脂肪敏感脂肪酶活性和棕色脂肪组织中解偶联蛋白-1 mRNA表达。这些发现表明，Y 5介导的肥胖可能涉及代谢变化，如脂肪分解和产热减少，以及摄食过多。因此，Y 5受体可以在调节能量稳态中发挥关键作用。
To clarify the role of the neuropeptide Y (NPY) Y5 receptor subtype in energy homeostasis, the effect of the intracerebroventricular infusion of a selective Y5 agonist, D-Trp (NPY)-N-34, was investigated in C57BL/6J mice. Intracerebroventricular infusion of D-Trp(34)NPY (5 and 10 mug/d) produced hyperphagia and body weight gain, accompanied by increased adipose tissue weight, hypercholesterolemia, hyperinsulinemia, and hyperleptinemia. Oral administration of a selective Y5 antagonist at a dose of 100 mg/kg twice a day completely suppressed all of these D-Trp(34)NPY-induced changes, indicating that chronic activation of the Y5 receptor produces hyperphagia and obesity. In addition, D-Trp(34)NPY still resulted in an increase in adipose tissue weight accompanied by hyperleptinemia and hypercholesterolemia, although D-Trp(34)NPY-induced food intake was restricted by pair-feeding. Under the pair-fed condition, D-Trp(34)NPY decreased hormone-sensitive lipase activity in white adipose tissue and uncoupling protein-1 mRNA expression in brown adipose tissue. These findings indicate that Y5-mediated obesity may involve metabolic changes, such as decreased lipolysis and thermogenesis, as well as hyperphagia. Therefore, the Y5 receptor can play a key role in regulating energy homeostasis.