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Orchestrated downregulation of genes involved in oxidative metabolic pathways in obese vs. lean high-fat young male consumers

机译:协调下调参与肥胖与氧化代谢途径相关的基因精瘦高脂肪的年轻男性消费者

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摘要

There are major variations in the susceptibility to weight gain among individuals undersimilar external influences (decreased physical activity and excessive calorie intake),depending on the genetic background. In the present study, we performed a microarrayanalysis and RT-PCR validations in order to find out differential gene expression insubcutaneous abdominal adipose tissue from two groups of subjects that despite livingin similar environmental conditions such as a habitual high fat dietary intake (energy asfat >40%) and similar moderate physical activity, some of them were successfully“resistant” (lean) to weight gain, while others were “susceptible” to fat deposition(obese). The classification of up- and down- regulated genes into different categoriestogether with the analysis of the altered biochemical pathways, revealed a coordinateddownregulation of catabolic pathways operating in the mitochondria: fatty acidoxidation (P=0.008), TCA cycle (P=0.001) and electron transport chain (P=0.012). Atthe same time, glucose metabolism (P=0.010) and fatty acid biosynthesis (P=0.011)pathways were also downregulated in obese compared to lean subjects. In conclusion,our data showed an orchestrated downregulation of nuclear-encoded mitochondrial geneexpression. These genes are involved in cellular respiration and oxidative metabolismpathways, and could play a role in the susceptibility to weight gain in some individuals.
机译:在相似的外部影响(体力活动减少和卡路里摄入过多)的影响下,个体对体重增加的敏感性差异很大,具体取决于遗传背景。在本研究中,我们进行了微阵列分析和RT-PCR验证,以找出两组受试者皮下腹部脂肪组织中的差异基因表达,这些受试者尽管生活在相似的环境条件下,例如习惯性高脂肪饮食摄入(能量脂肪> 40 %)和类似的中等体力活动,其中一些对体重增加成功“抵抗”(瘦),而另一些对脂肪沉积(肥胖)“敏感”。将上调和下调的基因分为不同类别,并分析了改变的生化途径,揭示了线粒体中分解代谢途径的协同下调:脂肪酸氧化(P = 0.008),TCA周期(P = 0.001) )和电子传输链(P = 0.012)。同时,与瘦人相比,肥胖者的葡萄糖代谢(P = 0.010)和脂肪酸生物合成(P = 0.011)途径也被下调。总而言之,我们的数据显示核编码的线粒体基因表达被精心策划的下调。这些基因参与细胞呼吸和氧化代谢途径,并可能在某些个体的体重增加易感性中起作用。

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