Intermittent energy restriction induces changes in breast gene expression and systemic metabolism.
Intermittent energy restriction induces changes in breast gene expression and systemic metabolism.
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DOI：
10.1186/s13058-016-0714-4
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发表时间：
2016-05-28
期刊：
影响因子：
--
通讯作者：
Howell A
中科院分区：
文献类型：
--
作者：
Harvie MN;Sims AH;Pegington M;Spence K;Mitchell A;Vaughan AA;Allwood JW;Xu Y;Rattray NJ;Goodacre R;Evans DG;Mitchell E;McMullen D;Clarke RB;Howell A
观察性研究表明，减肥和限制能量可以降低患乳腺癌的风险。间歇性能量限制 (IER) 减轻体重的程度与连续能量限制 (CER) 相同或更高，但 IER 对正常乳腺组织和全身代谢作为乳腺癌风险指标的影响尚不清楚。我们使用 Affymetrix GeneChips 评估了一个月经周期 IER（每周 2 天 65% 能量限制）对乳腺组织基因表达、形态测量脂肪细胞大小以及 23 名乳腺癌高危超重绝经前女性的全身代谢（胰岛素抵抗、脂质、血清和尿液代谢物、淋巴细胞基因表达）的影响。对 20 名受试者进行了匹配的 IER 活检前后的无监督和监督分析，同时采用液相和气相色谱质谱法评估了 IER 两天限制和五天非限制后所有受试者血清和尿液代谢物的相应变化。女性体重减少了 4.8% (±2.0%)，全身脂肪减少了 8.0% (±5.0%)。胰岛素抵抗（稳态模型评估 (HOMA)）在 IER 的限制日减少了 29.8% (±17.8%)，在不受限制的天减少了 11% (±34%)。在 IER 的两天限制期间，有 527 种代谢物显着增加或减少。正常饮食 5 天后，其中 91% 的人恢复到基线。 11 名受试者 (55%) 表现出与能量限制相关的代谢基因途径的减少，包括脂质合成、糖异生和糖原合成。其中一些女性的乳腺上皮细胞分化相关基因（分泌球蛋白、乳蛋白和粘蛋白）也增加，胶原蛋白合成减少（TNMD、PCOLCE2、TIMP4）。 IER 对其他 9 名受试者的乳腺基因表达没有明显影响。这些组在体重、全身脂肪、脂肪细胞大小或血清或尿液代谢组标记物的变化程度上没有差异。外周血淋巴细胞中未观察到相应的基因变化。乳腺组织中对 IER 的转录反应是可变的，这并未反映在所有受试者中发生的全身反应中。乳房反应性/无反应性的机制需要进一步研究。 ISRCTN77916487 31/07/2012。本文的在线版本 (doi:10.1186/s13058-016-0714-4) 包含补充材料，可供授权用户使用。
Observational studies suggest weight loss and energy restriction reduce breast cancer risk. Intermittent energy restriction (IER) reduces weight to the same extent as, or more than equivalent continuous energy restriction (CER) but the effects of IER on normal breast tissue and systemic metabolism as indicators of breast cancer risk are unknown. We assessed the effect of IER (two days of 65 % energy restriction per week) for one menstrual cycle on breast tissue gene expression using Affymetrix GeneChips, adipocyte size by morphometry, and systemic metabolism (insulin resistance, lipids, serum and urine metabolites, lymphocyte gene expression) in 23 overweight premenopausal women at high risk of breast cancer. Unsupervised and supervised analyses of matched pre and post IER biopsies in 20 subjects were performed, whilst liquid and gas chromatography mass spectrometry assessed corresponding changes in serum and urine metabolites in all subjects after the two restricted and five unrestricted days of the IER. Women lost 4.8 % (±2.0 %) of body weight and 8.0 % (±5.0 %) of total body fat. Insulin resistance (homeostatic model assessment (HOMA)) reduced by 29.8 % (±17.8 %) on the restricted days and by 11 % (±34 %) on the unrestricted days of the IER. Five hundred and twenty-seven metabolites significantly increased or decreased during the two restricted days of IER. Ninety-one percent of these returned to baseline after 5 days of normal eating. Eleven subjects (55 %) displayed reductions in energy restriction-associated metabolic gene pathways including lipid synthesis, gluconeogenesis and glycogen synthesis. Some of these women also had increases in genes associated with breast epithelial cell differentiation (secretoglobulins, milk proteins and mucins) and decreased collagen synthesis (TNMD, PCOLCE2, TIMP4). There was no appreciable effect of IER on breast gene expression in the other nine subjects. These groups did not differ in the degree of changes in weight, total body fat, fat cell size or serum or urine metabolomic markers. Corresponding gene changes were not seen in peripheral blood lymphocytes. The transcriptional response to IER is variable in breast tissue, which was not reflected in the systemic response, which occurred in all subjects. The mechanisms of breast responsiveness/non-responsiveness require further investigation. ISRCTN77916487 31/07/2012. The online version of this article (doi:10.1186/s13058-016-0714-4) contains supplementary material, which is available to authorized users.
影响因子：
8.8
作者：
Grieve, R J;Woods, K L;Mann, P R;Smith, S C;Wilson, G D;Howell, A
通讯作者：
Howell, A