期刊
FASEB JOURNAL
卷 19, 期 10, 页码 1680-+出版社
WILEY
DOI: 10.1096/fj.04-3434fje
关键词
neuropeptide Y; hypothalamic arcuate nucleus; food intake regulation; neuroendocrinology; gut hormone
资金
- National Institute for Health Research [03/DHCS/03/G121/48] Funding Source: researchfish
Agouti-related protein ( AgRP) and neuropeptide Y ( NPY) are colocalized in arcuate nucleus ( arcuate) neurons implicated in the regulation of energy balance. Both AgRP and NPY stimulate food intake when administered into the third ventricle and are up- regulated in states of negative energy balance. However, mice with targeted deletion of either NPY or AgRP or both do not have major alterations in energy homeostasis. Using bacterial artificial chromosome ( BAC) transgenesis we have targeted expression of a neurotoxic CAG expanded form of ataxin- 3 to AgRP- expressing neurons in the arcuate. This resulted in a 47% loss of AgRP neurons by 16 weeks of age, a significantly reduced body weight, ( wild- type mice ( WT) 34.7 +/- 0.7 g vs. transgenic mice ( Tg) 28.6 +/- 0.6 g, P < 0.001), and reduced food intake ( WT 5.0 +/- 0.2 vs. Tg 3.6 +/- 0.1 g per day, P < 0.001). Transgenic mice had significantly reduced total body fat, plasma insulin, and increased brown adipose tissue UCP1 expression. Transgenic mice failed to respond to peripherally administered ghrelin but retained sensitivity to PYY 3- 36. These data suggest that postembryonic partial loss of AgRP/ NPY neurons leads to a lean, hypophagic phenotype.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据