Bio-informatics analysis of a gene co-expression module in adipose tissue containing the diet-responsive gene Nnat.
Bio-informatics analysis of a gene co-expression module in adipose tissue containing the diet-responsive gene Nnat.
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对脂肪组织中含有饮食反应基因 Nnat 的基因共表达模块进行生物信息学分析。
DOI：
10.1186/1752-0509-4-175
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发表时间：
2010-12-27
影响因子：
--
通讯作者：
Scott J
中科院分区：
文献类型：
--
作者：
Li X;Thomason PA;Withers DJ;Scott J
肥胖会导致靶组织--骨骼肌、脂肪组织、肝脏和大脑--出现胰岛素抵抗。胰岛素抵抗易患2型糖尿病(T2D)和心血管疾病(CVD)。脂肪组织炎症是肥胖和胰岛素抵抗的基本特征。神经元抑素(Neuronatin，NNAT)在多种炎症或代谢紊乱状态下的表达发生改变，但其在脂肪组织、脑、胰岛等组织中的生理作用和调控机制尚不清楚。我们鉴定了在NNAT启动子中保守的转录因子结合位点(TFBS)，以及在脂肪组织中大量表达的转录因子(TF)。这些转录因子包括与调控有关的转录因子：脂肪生成(PPARγ，KLF15，IRF1，Creb1，Egr2，GATA3)；脂肪生成(MLXIP1，Srebp1c)；炎症(Jun，STAT3)；胰岛素信号与糖尿病易感性(Foxo1，TCF7L2)。我们还确定了NeuroD1是唯一有文献记载的控制NNAT表达的转运蛋白。我们发现KEGG途径与NNAT的表达显著相关，包括与炎症呈正相关，与代谢途径(尤其是氧化磷酸化、糖酵解和糖异生、丙酮酸代谢)和蛋白质周转呈负相关。共鉴定了27个与氧化应激有关的基因，包括与氧化应激有关的GSTT1和Sod3，与炎症有关的Sncg和Cxcl9，与脂肪形成有关的EBF1、Lgals12和Fzd4，它们与NNAT的表达存在协同变化，并在它们的启动子上发现了保守的转录因子结合位点。与这些基因中的每一个相关的功能网络被确定。我们的分析表明，NNAT是白色脂肪组织和下丘脑中的一个急性饮食反应基因，它可能在代谢、脂肪生成以及应对过量饮食的氧化应激和炎症反应中发挥重要作用。
Obesity causes insulin resistance in target tissues - skeletal muscle, adipose tissue, liver and the brain. Insulin resistance predisposes to type-2 diabetes (T2D) and cardiovascular disease (CVD). Adipose tissue inflammation is an essential characteristic of obesity and insulin resistance. Neuronatin (Nnat) expression has been found to be altered in a number of conditions related to inflammatory or metabolic disturbance, but its physiological roles and regulatory mechanisms in adipose tissue, brain, pancreatic islets and other tissues are not understood. We identified transcription factor binding sites (TFBS) conserved in the Nnat promoter, and transcription factors (TF) abundantly expressed in adipose tissue. These include transcription factors concerned with the control of: adipogenesis (Pparγ, Klf15, Irf1, Creb1, Egr2, Gata3); lipogenesis (Mlxipl, Srebp1c); inflammation (Jun, Stat3); insulin signalling and diabetes susceptibility (Foxo1, Tcf7l2). We also identified NeuroD1 the only documented TF that controls Nnat expression. We identified KEGG pathways significantly associated with Nnat expression, including positive correlations with inflammation and negative correlations with metabolic pathways (most prominently oxidative phosphorylation, glycolysis and gluconeogenesis, pyruvate metabolism) and protein turnover. 27 genes, including; Gstt1 and Sod3, concerned with oxidative stress; Sncg and Cxcl9 concerned with inflammation; Ebf1, Lgals12 and Fzd4 involved in adipogenesis; whose expression co-varies with Nnat were identified, and conserved transcription factor binding sites identified on their promoters. Functional networks relating to each of these genes were identified. Our analysis shows that Nnat is an acute diet-responsive gene in white adipose tissue and hypothalamus; it may play an important role in metabolism, adipogenesis, and resolution of oxidative stress and inflammation in response to dietary excess.
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影响因子：
29
作者：
Eguchi, Jun;Yan, Qing-Wu;Rosen, Evan D.
通讯作者：
Rosen, Evan D.
影响因子：
4.4
作者：
Evans, HK;Wylie, AA;Jirtle, RL
通讯作者：
Jirtle, RL
影响因子：
2.7
作者：
John, RM;Aparicio, SAJR;Surani, MA
通讯作者：
Surani, MA
DOI：
10.1073/pnas.0707797104
发表时间：
2007-10-16
影响因子：
11.1
作者：
Kim, Suyeon;Huang, Li-Wen;Barak, Yaacov
通讯作者：
Barak, Yaacov
影响因子：
64.5
作者：
Sing, Angela;Pannell, Dylan;Cordes, Sabine P.
通讯作者：
Cordes, Sabine P.