The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways.
The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways.
复制标题
卡路里限制的分级水平的影响：vi。短期渐变卡路里限制对下丘脑饥饿和昼夜节律信号通路的转录组反应的影响。
DOI：
10.18632/aging.100895
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发表时间：
2016-04
期刊：
影响因子：
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通讯作者：
Douglas A
中科院分区：
文献类型：
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作者：
Derous D;Mitchell SE;Green CL;Chen L;Han JD;Wang Y;Promislow DE;Lusseau D;Speakman JR;Douglas A
食物摄入和昼夜节律受下丘脑神经肽和循环激素的调节，这可能介导热量限制（CR）的抗衰老作用。我们通过定量暴露于分级水平的CR（10%至40%）3个月的雄性C57 BL/6小鼠的下丘脑转录物来测试这两种信号传导途径是否介导CR。我们发现，分级CR操作导致核心昼夜节律基因的上调，这与瘦素、胰岛素样生长因子1（IGF-1）、胰岛素和肿瘤坏死因子α（TNF-α）的循环水平呈负相关。此外，饥饿信号通路中的关键成分以反映更高限制水平下饥饿感升高的方式表达，并且也与胰岛素、TNF-α、瘦素和IGF-1的循环水平呈负相关。最后，食物预期活动和体温等表型与饥饿基因和核心时钟基因的表达水平相关。我们的研究结果表明，调节饥饿和昼夜信号通路，以响应循环激素水平的改变，这些激素本身是CR治疗引起的形态学变化的下游，可能是CR反应的重要因素，推动了一些关键的表型结果。
Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti‐ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin‐like growth factor 1 (IGF‐1), insulin, and tumor necrosis factor alpha (TNF‐α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF‐α, leptin and IGF‐1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.