Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index:: possible mode of function
Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index:: possible mode of function
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DOI：
10.1016/j.regpep.2004.10.011
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发表时间：
2005-04-15
影响因子：
--
通讯作者：
Wahlestedt, C
中科院分区：
文献类型：
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作者：
Ding, B;Kull, B;Wahlestedt, C
神经肽Y （NPY）参与控制食物摄入和能量平衡，这是基于对动物的许多观察。我们研究了人类NPY基因调控和编码序列中的单核苷酸多态性（snp）。其中一种变异（1128 T b> C）导致NPY信号肽密码子7处的氨基酸从亮氨酸变为脯氨酸，在瑞典两个独立的正常和超重人群中，这种变异与体重指数（BMI）增加有关。体外转录和翻译研究表明，这种信号肽的变化不太可能影响裂解位点和NPY进入内质网（ER）的靶向或摄取。然而，突变体和野生型的信号肽本身显著增强了NPY诱导的食物摄入，以及下丘脑NPY受体信号传导。我们在人类中的研究结果强烈表明，NPY信号系统与体重调节有关，并提示信号肽具有新的和意想不到的功能作用。(C) 2004 Elsevier B.V.版权所有
Neuropeptide Y (NPY) has been implicated in the control of food intake and energy balance based on many observations in animals. We have studied single nucleotide polymorphisms (SNPs) within the regulatory and coding sequences of the human NPY gene. One variant (1128 T>C), which causes an amino acid change from leucine to proline at codon 7 in the signal peptide of NPY, was associated with increased body mass index (BMI) in two separate Swedish populations of normal and overweight individuals. In vitro transcription and translation studies indicated the unlikelihood that this signal peptide variation affects the site of cleavage and targeting or uptake of NPY into the endoplasmic reticulum (ER). However, the mutant, and to a lesser extent the wild-type, signal peptide by themselves markedly potentiated NPY-induced food intake, as well as hypothalamic NPY receptor signaling. Our findings in humans strongly indicate that the NPY signaling system is implicated in body weight regulation and suggest a new and unexpected functional role of a signal peptide. (C) 2004 Elsevier B.V. All rights reserved.