Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice
Remodeling of the arcuate nucleus energy-balance circuit is inhibited in obese mice
复制标题
DOI：
10.1172/jci43134
复制
发表时间：
2012-01-01
影响因子：
15.9
通讯作者：
Flier, Jeffrey S.
中科院分区：
文献类型：
--
作者：
McNay, David E. G.;Briancon, Nadege;Flier, Jeffrey S.
在中枢神经系统中，下丘脑弓状核（ARN）能量平衡回路在调节体重中起着关键作用。最近的研究表明，神经发生发生在成人下丘脑，揭示了ARN能量平衡回路比最初认为的更具可塑性。饮食的改变导致ARN中基因表达和神经元活性的改变，其中一些可能反映了下丘脑的可塑性。为了探索这种可能性，我们研究了继发于高脂饮食（HFD）消耗或瘦素缺乏的肥胖小鼠下丘脑神经元的周转。我们发现ARN中神经元的大量周转导致了持续的细胞重塑。喂食HFD的小鼠抑制了神经发生，正如观察到的那样，这些小鼠产生的新神经元更少，保留的旧神经元更多。这种神经元更新的抑制与新生神经元的凋亡增加有关。缺乏瘦素的小鼠产生的新神经元也较少，这一观察结果部分解释了下丘脑神经干细胞的损失。这些数据表明，有大量的弓形神经元回路在小鼠出生后的营业额，并揭示了意想不到的能力，饮食和瘦素缺乏症，以抑制这种神经元重塑。这一见解对我们理解能量平衡和大脑功能的营养调节具有重要意义。
In the CNS, the hypothalamic arcuate nucleus (ARN) energy-balance circuit plays a key role in regulating body weight. Recent studies have shown that neurogenesis occurs in the adult hypothalamus, revealing that the ARN energy-balance circuit is more plastic than originally believed. Changes in diet result in altered gene expression and neuronal activity in the ARN, some of which may reflect hypothalamic plasticity. To explore this possibility, we examined the turnover of hypothalamic neurons in mice with obesity secondary to either high-fat diet (HFD) consumption or leptin deficiency. We found substantial turnover of neurons in the ARN that resulted in ongoing cellular remodeling. Feeding mice HFD suppressed neurogenesis, as demonstrated by the observation that these mice both generated fewer new neurons and retained more old neurons. This suppression of neuronal turnover was associated with increased apoptosis of newborn neurons. Leptin-deficient mice also generated fewer new neurons, an observation that was explained in part by a loss of hypothalamic neural stem cells. These data demonstrate that there is substantial postnatal turnover of the arcuate neuronal circuitry in the mouse and reveal the unexpected capacity of diet and leptin deficiency to inhibit this neuronal remodeling. This insight has important implications for our understanding of nutritional regulation of energy balance and brain function.