Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism

Transcriptome analysis of peripheral blood mononuclear cells in human subjects following a 36 h fast provides evidence of effects on genes regulating inflammation, apoptosis and energy metabolism
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DOI:
10.1007/s12263-014-0432-4
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发表时间:
2014-11-01
影响因子:
3.5
通讯作者:
Johnson, I. T.
Johnson, I. T.
中科院分区:
医学2区
文献类型:
--
作者:
Elliott, R. M.;de Roos, B.;Johnson, I. T.

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人们对定期禁食的饮食的潜在健康益处越来越感兴趣。虽然动物研究提供了令人信服的证据,证明隔日禁食等喂养模式可以延长寿命并降低许多慢性疾病的发病率,但人类研究的证据则更加有限和模棱两可。此外,尽管已经提出了几个候选过程,以促进在动物中观察到的健康益处,但负责的精确分子机制仍有待阐明。本文所述的研究检查了延长禁食对10名明显健康受试者外周血单核细胞基因转录谱的影响,比较了过夜禁食后的转录谱,每周间隔4次采样,与禁食24小时后观察到的单次转录谱。整夜禁食数据分析显示存在显著的个体间差异,其中一些差异与性别和受试者体重等参数相关。例如,观察到体重指数与受1型干扰素调节的基因表达之间存在显著的正相关。延长禁食后观察到相对细微的变化。尽管如此,变化模式与脂肪酸氧化刺激、细胞周期和凋亡改变以及关键促炎基因表达降低一致。脂肪酸氧化的刺激是禁食的预期反应,最有可能在所有组织中。强调的其他过程提供了可能有助于人类间歇性禁食的假定有益作用的潜在机制的迹象。
There is growing interest in the potential health benefits of diets that involve regular periods of fasting. While animal studies have provided compelling evidence that feeding patterns such as alternate-day fasting can increase longevity and reduce incidence of many chronic diseases, the evidence from human studies is much more limited and equivocal. Additionally, although several candidate processes have been proposed to contribute to the health benefits observed in animals, the precise molecular mechanisms responsible remain to be elucidated. The study described here examined the effects of an extended fast on gene transcript profiles in peripheral blood mononuclear cells from ten apparently healthy subjects, comparing transcript profiles after an overnight fast, sampled on four occasions at weekly intervals, with those observed on a single occasion after a further 24 h of fasting. Analysis of the overnight fasted data revealed marked inter-individual differences, some of which were associated with parameters such as gender and subject body mass. For example, a striking positive association between body mass index and the expression of genes regulated by type 1 interferon was observed. Relatively subtle changes were observed following the extended fast. Nonetheless, the pattern of changes was consistent with stimulation of fatty acid oxidation, alterations in cell cycling and apoptosis and decreased expression of key pro-inflammatory genes. Stimulation of fatty acid oxidation is an expected response, most likely in all tissues, to fasting. The other processes highlighted provide indications of potential mechanisms that could contribute to the putative beneficial effects of intermittent fasting in humans.