Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid β-oxidation:: functional role of peroxisome proliferator-activated receptor α in human peripheral blood mononuclear cells
Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid β-oxidation:: functional role of peroxisome proliferator-activated receptor α in human peripheral blood mononuclear cells
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DOI：
10.1093/ajcn/86.5.1515
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发表时间：
2007-11-01
影响因子：
7.1
通讯作者：
Muller, Michael
中科院分区：
文献类型：
--
作者：
Bouwens, Mark;Afman, Lydia A.;Muller, Michael
背景：外周血单个核细胞（PBMC）是健康人体中唯一容易获得的细胞。各种研究表明，疾病特征的基因表达模式在PBMC中。然而，营养对PBMC基因表达模式的影响知之甚少。脂肪酸是通过激活核受体过氧化物酶体增殖物激活受体α（PPAR α）来调节基因表达的营养物质。PBMC表达过氧化物酶体增殖物激活受体α，使这些细胞有趣的研究FA依赖的基因expression.Objective：本研究的目的是阐明PBMC基因表达谱是否也反映营养相关的代谢变化。此外，我们专注于特定的作用，过氧化物酶体增殖物激活物激活物受体α调节PBMC基因表达在禁食期间，当血浆游离脂肪酸是higher.Design：4名健康男性志愿者禁食48小时。将PBMC RNA在Affyphin全基因组微阵列上杂交。为探讨过氧化物酶体增殖物激活受体α（PPAR α）的作用，将9名献血员的PBMC与特异性配体Wy14643共同孵育。结果：禁食24和48 h后，分别有1200和1386个基因发生了1.4倍以上的变化。其中许多基因参与脂肪酸β-氧化，是已知的PPAR α靶基因。孵育的P13 MCs与Wy14643导致在上调的基因，也上调在fasting.Conclusions：我们得出结论，PBMC基因表达谱反映营养相关的代谢变化，如禁食和部分禁食诱导的变化可能是由过氧化物酶体增殖物激活受体α调节。
Background: Peripheral blood mononuclear cells (PBMCs) are the only readily available cells in healthy humans. Various studies showed disease-characteristic gene expression patterns in PBMCs. However, little is known of nutritional effects on PBMC gene expression patterns. Fatty acids are nutrients that regulate gene expression by activating the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR alpha). PBMCs express PPAR alpha, making these cells interesting to study FA-dependent gene expression.Objective: The aim of this study was to elucidate whether PBMC gene expression profiles also reflect nutrition-related metabolic changes. Furthermore, we focused on the specific role of PPAR alpha in regulation of PBMC gene expression during fasting, when plasma free fatty acids are elevated.Design: Four healthy male volunteers fasted for 48 h. PBMC RNA was hybridized on Affymetrix whole genome microarrays. To elucidate the role of PPAR alpha, PBMCs of 9 blood donors were incubated with the specific PPAR alpha ligand Wy14643.Results: After 24 and 48 h of fasting, 1200 and 1386 genes were changed > 1.4-fold, respectively. Many of those genes were involved in fatty acid beta-oxidation and are known PPAR alpha target genes. Incubation of P13MCs with Wy14643 resulted in up-regulation of genes that were also up-regulated during fasting.Conclusions: We conclude that PBMC gene expression profiles reflect nutrition-related metabolic changes such as fasting and that part of the fasting-induced changes are likely regulated by PPAR alpha.