Activation of Dorsomedial Hypothalamic Neurons Promotes Physical Activity and Decreases Food Intake and Body Weight in Zucker Fatty Rats.
Activation of Dorsomedial Hypothalamic Neurons Promotes Physical Activity and Decreases Food Intake and Body Weight in Zucker Fatty Rats.
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DOI：
10.3389/fnmol.2018.00179
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发表时间：
2018
影响因子：
4.8
通讯作者：
Bi S
中科院分区：
文献类型：
--
作者：
Zhang N;Yang L;Guo L;Bi S
以前的报告表明，在各种肥胖动物模型中，跑轮运动或自愿锻炼可以防止过度吞噬和肥胖，但这种影响似乎只有在缺乏瘦素或瘦素受体的肥胖动物中才微乎其微。这种无效性背后的机制仍不清楚。在这里，我们利用瘦素受体突变体肥胖Zucker(Lepr(Fa)，Zf)和Koletsky(Lepr(FAK)，SHROB)大鼠确定了下丘脑背内侧(DMH)神经元激活在调节体力活动、食物摄入量和体重中的作用。随机性喂养的SHROB大鼠旋转轮锁定后，出现巨噬细胞增多，体重迅速增加。这些改变在自愿使用跑轮的随机喂养的SHROB大鼠中没有得到改善，但当它们配对喂养到瘦肉对照组的消耗量时，使用跑轮的SHROB大鼠的体重显著减少。下丘脑基因表达的测定显示，久坐不动的SHROB大鼠弓状核(ARC)神经肽Y(NPY)表达增加，阿片黑素皮质素原(POMC)表达减少。在跑步和配对饲养条件下，ARC NPY和POMC的表达都发生了进一步的变化，这表明这两个基因都受到适当的调控，以响应跑步活动和食物限制引起的能量需求增加或变化。值得注意的是，c-Fos免疫组织化学显示，尽管自愿跑步活动增加了正常大鼠DMH(特别是腹侧和尾侧亚区)c-Fos阳性细胞的数量，但在ZF大鼠中没有观察到这种激活。用腺相关病毒(AAV)介导的设计受体hM3D(GQ)在ZF大鼠的腹侧和尾侧DMH中的表达，我们发现通过注射设计药物氯氮平(CNO)来化学刺激这些DMH亚区的神经元显著增加它们的跑步活动，减少它们的摄食量和体重。总之，这些结果表明，腹侧和尾侧DMH神经元的激活促进了身体活动，减少了食物摄入量和体重，并表明完整的DMH神经信号可能是运动导致缺乏瘦素受体的肥胖大鼠减少食物摄入量和体重的关键。
Previous reports have shown that running wheel activity or voluntary exercise prevents hyperphagia and obesity in various animal models of obesity, but such effects seem only minimal in obese animals lacking leptin or leptin receptors. The mechanisms underlying this ineffectiveness remain unclear. Here, we identified the action of neuronal activation in the dorsomedial hypothalamus (DMH) in modulating physical activity, food intake and body weight using leptin receptor mutant obese Zucker (Lepr(fa), ZF) and Koletsky (Lepr(fak), SHROB) rats. Ad lib-fed SHROB rats with locked running wheels became hyperphagic and gained body weight rapidly. These alterations were not ameliorated in ad lib-fed SHROB rats with voluntary access to running wheels, but the body weight of SHROB rats with running wheel access was significantly decreased when they were pair-fed to the amounts consumed by lean controls. Determinations of hypothalamic gene expression revealed that sedentary ad lib-fed SHROB rats had increased expression of neuropeptide Y (Npy) and decreased expression of pro-opiomelanocortin (Pomc) in the arcuate nucleus (ARC). Both ARC Npy and Pomc expression were further altered under running and pair-fed conditions, indicating that both genes are appropriately regulated in response to increased energy demands or alterations caused by running activity and food restriction. Strikingly, c-Fos immunohistochemistry revealed that while voluntary running activity elevated the number of c-Fos positive cells in the DMH (particularly in the ventral and caudal subregions) of intact rats, such activation was not observed in ZF rats. Using adeno-associated virus (AAV)-mediated expression of the designer receptors hM3D(Gq) in the ventral and caudal DMH of ZF rats, we found that chemogenetic stimulation of neurons in these DMH subregions via injection of the designer drug clozapine N-oxide (CNO) significantly increased their running activity and reduced their food intake and body weight. Together, these results demonstrate that activation of ventral and caudal DMH neurons promotes physical activity and decreases food intake and body weight and suggest that intact DMH neural signaling is likely crucial for exercise-induced reductions of food intake and body weight in obese rats lacking leptin receptors.
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DOI：
10.1073/pnas.0700293104
发表时间：
2007-03-20
影响因子：
11.1
作者：
Armbruster, Blaine N.;Li, Xiang;Roth, Bryan L.
通讯作者：
Roth, Bryan L.
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
影响因子：
29
作者：
Dodd GT;Worth AA;Nunn N;Korpal AK;Bechtold DA;Allison MB;Myers MG Jr;Statnick MA;Luckman SM
通讯作者：
Luckman SM
影响因子：
2.9
作者：
Bi S
通讯作者：
Bi S
影响因子：
3.3
作者：
BERNARDIS, LL
通讯作者：
BERNARDIS, LL