Diurnal rhythms in the white adipose tissue transcriptome are disturbed in obese individuals with type 2 diabetes compared with lean control individuals
Diurnal rhythms in the white adipose tissue transcriptome are disturbed in obese individuals with type 2 diabetes compared with lean control individuals
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与瘦对照个体相比，肥胖 2 型糖尿病个体的白色脂肪组织转录组的昼夜节律受到干扰
DOI：
10.1007/s00125-019-4813-5
复制
发表时间：
2019
期刊：
影响因子：
8.2
通讯作者：
P. Bisschop
中科院分区：
文献类型：
--
作者：
D. J. Stenvers;A. Jongejan;S. Atiqi;J. Vreijling;E. J. Limonard;E. Endert;F. Baas;P. Moerland;E. Fliers;A. Kalsbeek;P. Bisschop
目的/假设动物研究表明，脂肪组织中时钟基因表达的昼夜节律紊乱可诱导肥胖和2型糖尿病。昼夜节律计时系统对能量代谢的重要性已经得到了很好的证实，但是对于肥胖2型糖尿病患者（时钟）基因表达的昼夜调节知之甚少。在这项研究中，我们的目的是确定关键的干扰昼夜节律的白色脂肪组织转录组在肥胖的个人与2型diabetes.MethodsIn病例对照设计，我们包括6个肥胖的个人与2型糖尿病和6个健康，精益控制个人。所有参与者每天在Zeitgeber时间（ZT，ZT 0：00代表开灯时间）0：30，6：00和11：30提供三顿相同的膳食，持续3天。在第2天ZT 15：30以及第3天ZT 0：15、ZT 5：45和ZT 11：15连续采集4份皮下腹部脂肪组织样本。使用RNA测序测量基因表达。结果与健康对照个体相比，2型糖尿病患者的核心时钟基因显示振幅振荡降低。此外，在2型糖尿病患者中，16，818个表达基因中只有1.8%（303个基因）显示出显著的昼夜节律性，而健康对照组中为8.4%（1421个基因）。富集分析显示，2型糖尿病患者中参与脂解调节的典型代谢途径的节律丧失。对2型糖尿病患者中具有改变的mesor的基因的富集分析显示，翻译起始途径“EIF 2信号”的活性降低。2型糖尿病患者表现出减少昼夜节律在餐后葡萄糖concentration.Conclusions/interpretationDiurnal时钟和代谢基因表达的节奏是减少在皮下脂肪组织的肥胖个体与2型糖尿病相比，瘦控制参与者。需要进一步的研究来探索我们研究确定的潜在治疗靶点，包括时钟增强和EIF 2信号传导的诱导。数据可用性用于节律表达分析和独创性途径分析的原始测序数据和补充文件已保存在NCBI Gene Express Omnibus（GEO系列登录号GSE 104674）中。
Aims/hypothesisAnimal studies have indicated that disturbed diurnal rhythms of clock gene expression in adipose tissue can induce obesity and type 2 diabetes. The importance of the circadian timing system for energy metabolism is well established, but little is known about the diurnal regulation of (clock) gene expression in obese individuals with type 2 diabetes. In this study we aimed to identify key disturbances in the diurnal rhythms of the white adipose tissue transcriptome in obese individuals with type 2 diabetes.MethodsIn a case–control design, we included six obese individuals with type 2 diabetes and six healthy, lean control individuals. All participants were provided with three identical meals per day for 3 days at zeitgeber time (ZT, with ZT 0:00 representing the time of lights on) 0:30, 6:00 and 11:30. Four sequential subcutaneous abdominal adipose tissue samples were obtained, on day 2 at ZT 15:30, and on day 3 at ZT 0:15, ZT 5:45 and ZT 11:15. Gene expression was measured using RNA sequencing.ResultsThe core clock genes showed reduced amplitude oscillations in the individuals with type 2 diabetes compared with the healthy control individuals. Moreover, in individuals with type 2 diabetes, only 1.8% (303 genes) of 16,818 expressed genes showed significant diurnal rhythmicity, compared with 8.4% (1421 genes) in healthy control individuals. Enrichment analysis revealed a loss of rhythm in individuals with type 2 diabetes of canonical metabolic pathways involved in the regulation of lipolysis. Enrichment analysis of genes with an altered mesor in individuals with type 2 diabetes showed decreased activity of the translation initiating pathway ‘EIF2 signaling’. Individuals with type 2 diabetes showed a reduced diurnal rhythm in postprandial glucose concentrations.Conclusions/interpretationDiurnal clock and metabolic gene expression rhythms are decreased in subcutaneous adipose tissue of obese individuals with type 2 diabetes compared with lean control participants. Future investigation is needed to explore potential treatment targets as identified by our study, including clock enhancement and induction of EIF2 signalling.Data availabilityThe raw sequencing data and supplementary files for rhythmic expression analysis and Ingenuity Pathway Analysis have been deposited in NCBI Gene Expression Omnibus (GEO series accession number GSE104674).
影响因子：
29
作者：
He B;Nohara K;Park N;Park YS;Guillory B;Zhao Z;Garcia JM;Koike N;Lee CC;Takahashi JS;Yoo SH;Chen Z
通讯作者：
Chen Z
影响因子：
29
作者：
Jacobi D;Liu S;Burkewitz K;Kory N;Knudsen NH;Alexander RK;Unluturk U;Li X;Kong X;Hyde AL;Gangl MR;Mair WB;Lee CH
通讯作者：
Lee CH
DOI：
10.1152/ajpendo.2001.280.1.e40
发表时间：
2001-01-01
影响因子：
5.1
作者：
Johnson, JA;Fried, SK;Albu, JB
通讯作者：
Albu, JB