Gene Expression Changes in Adipose Tissue with Diet- and/or Exercise-Induced Weight Loss
Gene Expression Changes in Adipose Tissue with Diet- and/or Exercise-Induced Weight Loss
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DOI：
10.1158/1940-6207.capr-12-0212
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发表时间：
2013-03-01
影响因子：
3.3
通讯作者：
Ulrich, Cornelia M.
中科院分区：
文献类型：
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作者：
Campbell, Kristin L.;Foster-Schubert, Karen E.;Ulrich, Cornelia M.
脂肪组织通过增加炎症因子、类固醇激素和改变的脂肪因子的产生，在肥胖相关癌症中发挥作用。减肥对脂肪组织基因表达的影响可能有助于了解肥胖与癌症风险之间的联系途径。我们在一项针对超重/肥胖绝经后女性的饮食、运动或饮食+运动相结合与对照的随机试验中进行了一项辅助研究。在 45 名女性中，在基线和 6 个月后进行了皮下脂肪组织活检，并通过微阵列（重点是预先指定的候选途径）以及对超过 37,000 个转录物的无监督聚类来确定脂肪组织基因表达的变化（Illumina）。首先按随机分组进行分析，然后按所有女性 6 个月时的体重变化程度进行分析。 6 个月时，节食、运动和节食+运动参与者平均减重 8.8、2.5 和 7.9 公斤（所有 P < 0.05 对比对照组没有变化）。干预组候选基因表达没有显着变化。按体重变化类别进行分析，体重减轻幅度越大，17β-羟基类固醇脱氢酶-1（HSD17B1，P-趋势 < 0.01）和瘦素（LEP，P-趋势 < 0.01）表达减少，雌激素受体-1（ESR1，P-趋势 = 0.08）和胰岛素样生长因子结合蛋白-3（IGFBP3，IGFBP3， P-趋势 = 0.08)。无监督聚类揭示了 83 个具有统计显着变化的转录本。多种基因表达变化与相关血清生物标志物的变化相关。体重减轻与 6 个月后脂肪组织基因表达的变化相关，尤其是与肥胖和癌症相关的两条途径，即类固醇激素代谢和 IGF 信号传导。癌症预防研究； 6(3)； 217-31。 (C) 2013 年 AACR。
Adipose tissue plays a role in obesity-related cancers via increased production of inflammatory factors, steroid hormones, and altered adipokines. The impact of weight loss on adipose tissue gene expression may provide insights into pathways linking obesity with cancer risk. We conducted an ancillary study within a randomized trial of diet, exercise, or combined diet + exercise versus control among overweight/obese postmenopausal women. In 45 women, subcutaneous adipose tissue biopsies were conducted at baseline and after 6 months, and changes in adipose tissue gene expression were determined by microarray with an emphasis on prespecified candidate pathways as well as by unsupervised clustering of more than 37,000 transcripts (Illumina). Analyses were conducted first by randomization group and then by degree of weight change at 6-months in all women combined. At 6 months, diet, exercise, and diet + exercise participants lost a mean of 8.8, 2.5, and 7.9 kg (all P < 0.05 vs. no change in controls). There was no significant change in candidate gene expression by intervention group. In analysis by weight change category, greater weight loss was associated a decrease in 17 beta-hydroxysteroid dehydrogenase-1 (HSD17B1, P-trend < 0.01) and leptin (LEP, P-trend < 0.01) expression, and marginally significant increased expression of estrogen receptor-1 (ESR1, P-trend = 0.08) and insulin-like growth factor-binding protein-3 (IGFBP3, P-trend = 0.08). Unsupervised clustering revealed 83 transcripts with statistically significant changes. Multiple gene expression changes correlated with changes in associated serum biomarkers. Weight loss was associated with changes in adipose tissue gene expression after 6 months, particularly in two pathways postulated to link obesity and cancer, that is, steroid hormone metabolism and IGF signaling. Cancer Prev Res; 6(3); 217-31. (C) 2013 AACR.