Circadian regulation in human white adipose tissue revealed by transcriptome and metabolic network analysis
Circadian regulation in human white adipose tissue revealed by transcriptome and metabolic network analysis
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DOI：
10.1038/s41598-019-39668-3
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发表时间：
2019-02-25
影响因子：
4.6
通讯作者：
Johnston, Jonathan D.
中科院分区：
文献类型：
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作者：
Christou, Skevoulla;Wehrens, Sophie M. T.;Johnston, Jonathan D.
研究大多数人体组织的昼夜节律由于收集系列样本的困难而受到阻碍。在这里，我们揭示了人类白色脂肪组织转录组和代谢途径的昼夜节律。皮下脂肪组织取自7名健康男性，在严格控制的“常规”条件下进行。每名参与者每隔六小时进行五次活组织检查，用于微阵列分析和电子计算机综合代谢模型。我们鉴定了837个显示昼夜节律表达谱的转录本(阵列上41619个靶向转录本探针中的2%)，转录本明显分开，在早上(258个探针)和晚上(579个探针)达到峰值。我们的节律转录本与已发表的动物脂肪和人类血液转录组数据只有部分重叠。早晨高峰转录本与基因表达调控、氮化合物代谢和核酸生物学有关；晚高峰转录本与有机酸代谢、辅因子代谢和氧化还原活性有关。在电子途径分析中，进一步表明了脂肪和核酸代谢的昼夜调节；它还预测了关键代谢途径的昼夜变化，如柠檬酸循环和支链氨基酸降解。综上所述，体内的昼夜节律存在于多种脂肪代谢途径中，包括那些与脂肪代谢有关的途径，以及细胞生物化学的核心方面。
Studying circadian rhythms in most human tissues is hampered by difficulty in collecting serial samples. Here we reveal circadian rhythms in the transcriptome and metabolic pathways of human white adipose tissue. Subcutaneous adipose tissue was taken from seven healthy males under highly controlled 'constant routine' conditions. Five biopsies per participant were taken at six-hourly intervals for microarray analysis and in silico integrative metabolic modelling. We identified 837 transcripts exhibiting circadian expression profiles (2% of 41619 transcript targeting probes on the array), with clear separation of transcripts peaking in the morning (258 probes) and evening (579 probes). There was only partial overlap of our rhythmic transcripts with published animal adipose and human blood transcriptome data. Morning-peaking transcripts associated with regulation of gene expression, nitrogen compound metabolism, and nucleic acid biology; evening-peaking transcripts associated with organic acid metabolism, cofactor metabolism and redox activity. In silico pathway analysis further indicated circadian regulation of lipid and nucleic acid metabolism; it also predicted circadian variation in key metabolic pathways such as the citric acid cycle and branched chain amino acid degradation. In summary, in vivo circadian rhythms exist in multiple adipose metabolic pathways, including those involved in lipid metabolism, and core aspects of cellular biochemistry.