Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity.
Knockdown of NPY expression in the dorsomedial hypothalamus promotes development of brown adipocytes and prevents diet-induced obesity.
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DOI：
10.1016/j.cmet.2011.02.019
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发表时间：
2011-05-04
期刊：
影响因子：
29
通讯作者：
Bi S
中科院分区：
文献类型：
--
作者：
Chao PT;Yang L;Aja S;Moran TH;Bi S
下丘脑神经肽Y （NPY）与能量平衡的控制有关，但NPY在下丘脑背内侧（DMH）中的生理重要性尚不清楚。在这里，我们报告了通过腺相关病毒介导的RNAi敲低DMH中NPY的表达，减少了喂食常规食物的大鼠的脂肪储存，并改善了高脂肪饮食诱导的贪食和肥胖。DMH NPY敲低可通过交感神经系统导致腹股沟白色脂肪组织中棕色脂肪细胞的形成。这种敲低增加了解偶联蛋白1在腹股沟脂肪和肩胛间棕色脂肪组织（BAT）中的表达。与BAT的激活一致，DMH NPY敲低增加了能量消耗，增强了对寒冷环境的产热反应。这种基因敲低也增加了运动活动，改善了葡萄糖稳态，增强了胰岛素敏感性。总之，这些结果表明DMH NPY通过影响食物摄入、体脂、产热、能量消耗和身体活动在体重调节中起关键作用。
Hypothalamic neuropeptide Y (NPY) has been implicated in control of energy balance, but the physiological importance of NPY in the dorsomedial hypothalamus (DMH) remains unclear. Here we report that knockdown of NPY expression in the DMH by adeno-associated virus-mediated RNAi reduced fat depots in rats fed regular chow and ameliorated high-fat diet-induced hyperphagia and obesity. DMH NPY knockdown resulted in development of brown adipocytes in inguinal white adipose tissue through the sympathetic nervous system. This knockdown increased uncoupling protein 1 expression in both inguinal fat and interscapular brown adipose tissue (BAT). Consistent with the activation of BAT, DMH NPY knockdown increased energy expenditure and enhanced the thermogenic response to a cold environment. This knockdown also increased locomotor activity, improved glucose homeostasis and enhanced insulin sensitivity. Together, these results demonstrate critical roles of DMH NPY in body weight regulation through affecting food intake, body adiposity, thermogenesis, energy expenditure and physical activity.
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影响因子：
--
作者：
BILLINGTON, CJ;BRIGGS, JE;LEVINE, AS
通讯作者：
LEVINE, AS
DOI：
10.1152/ajpregu.00805.2004
发表时间：
2005-06-01
影响因子：
2.8
作者：
Kawaguchi, M;Scott, KA;Bi, S
通讯作者：
Bi, S
DOI：
10.1111/j.1748-1716.1970.tb04759.x
发表时间：
1970-01-01
期刊：
ACTA PHYSIOLOGICA SCANDINAVICA
影响因子：
--
作者：
FREDHOLM, BB;OBERG, B;ROSELL, S
通讯作者：
ROSELL, S
影响因子：
--
作者：
Kesterson, RA;Huszar, D;Cone, RD
通讯作者：
Cone, RD
DOI：
10.1152/ajpregu.00041.2006
发表时间：
2006-07-01
影响因子：
2.8
作者：
Aja, Susan;Bi, Sheng;McFadden, Jill M.
通讯作者：
McFadden, Jill M.