Transcriptional profiling of hypothalamus during development of adiposity in genetically selected fat and lean chickens
Transcriptional profiling of hypothalamus during development of adiposity in genetically selected fat and lean chickens
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DOI：
10.1152/physiolgenomics.00029.2010
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发表时间：
2010-07-01
影响因子：
4.6
通讯作者：
Porter, Tom E.
中科院分区：
文献类型：
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作者：
Byerly, Mardi S.;Simon, Jean;Porter, Tom E.
Byerly MS，Simon J，Cogburn LA，Le Bihan-Duval E，Duclos MJ，Aggrey SE，Porter TE.遗传选择的肥鸡和瘦鸡肥胖发生过程中下丘脑的转录谱。Physiol Genomics 42：157-167，2010.首次发表于2010年4月6日; doi：10.1152/physiolgenomics.00029.2010.-下丘脑整合外周信号以调节脊椎动物的食物摄入、能量代谢，并最终调节生长速率和身体组成。下丘脑调节控制的偏差可导致多余的身体脂肪的积累。参与这一过程的许多调控基因仍然没有确定，比较研究可能有助于解开控制体重和食物摄入的进化保守机制。在本研究中，不同选择的脂肪（FL）和瘦（LL）线的鸡被用来表征这些独特的遗传线，在没有差异的食物摄入量或体重的肥胖症的差异下丘脑基因表达的差异。下丘脑转录谱的定义与cDNA微阵列之间的肥胖分歧之前和期间的两个线。在鸡中鉴定的六个差异表达基因与转基因或敲除小鼠中与体脂控制相关的基因相关，支持这些基因在物种间的重要性。我们确定了参与葡萄糖代谢的9个基因的表达差异，表明下丘脑糖酵解的改变可能导致基因型之间体脂水平的差异。甜味受体（TAS 1 R1）的表达，这在哺乳动物中参与葡萄糖传感和能量摄取，也较高的FL鸡，这表明葡萄糖传感的早期差异可能会改变设定点为随后的身体组成。与肿瘤坏死因子（TNF）信号相关的基因表达的差异也被注意到。总之，我们确定了下丘脑内的转录和代谢过程的改变，这可能有助于在食物摄入量没有差异的情况下FL鸡体内脂肪的过度积累，从而有助于该禽类模型中肥胖的遗传基础。
Byerly MS, Simon J, Cogburn LA, Le Bihan-Duval E, Duclos MJ, Aggrey SE, Porter TE. Transcriptional profiling of hypothalamus during development of adiposity in genetically selected fat and lean chickens. Physiol Genomics 42: 157-167, 2010. First published April 6, 2010; doi: 10.1152/physiolgenomics.00029.2010.-The hypothalamus integrates peripheral signals to regulate food intake, energy metabolism, and ultimately growth rate and body composition in vertebrates. Deviations in hypothalamic regulatory controls can lead to accumulation of excess body fat. Many regulatory genes involved in this process remain unidentified, and comparative studies may be helpful to unravel evolutionarily conserved mechanisms controlling body weight and food intake. In the present study, divergently selected fat (FL) and lean (LL) lines of chickens were used to characterize differences in hypothalamic gene expression in these unique genetic lines that develop differences in adiposity without differences in food intake or body weight. Hypothalamic transcriptional profiles were defined with cDNA microarrays before and during divergence of adiposity between the two lines. Six differentially expressed genes identified in chickens are related to genes associated with control of body fat in transgenic or knockout mice, supporting the importance of these genes across species. We identified differences in expression of nine genes involved in glucose metabolism, suggesting that alterations in hypothalamic glycolysis might contribute to differences in levels of body fat between genotypes. Expression of the sweet taste receptor (TAS1R1), which in mammals is involved in glucose sensing and energy uptake, was also higher in FL chickens, suggesting that early differences in glucose sensing might alter the set point for subsequent body composition. Differences in expression of genes associated with tumor necrosis factor (TNF) signaling were also noted. In summary, we identified alterations in transcriptional and metabolic processes within the hypothalamus that could contribute to excessive accumulation of body fat in FL chickens in the absence of differences in food intake, thereby contributing to the genetic basis for obesity in this avian model.