Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats

Genistein reduced insulin resistance index through modulating lipid metabolism in ovariectomized rats
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DOI:
10.1016/j.nutres.2012.10.002
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发表时间:
2012-11-01
期刊:
影响因子:
4.5
通讯作者:
Song, Jihyun
Song, Jihyun
中科院分区:
医学3区
文献类型:
--
作者:
Choi, Joo Sun;Koh, In-Uk;Song, Jihyun

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由于雌激素的下降,绝经后妇女患肥胖和胰岛素抵抗的风险更高,但染料木素(一种植物雌激素)可能降低这些与饮食有关的疾病的风险。在这项研究中,我们假设补充染料木素通过调节脂质代谢对去卵巢大鼠模型的胰岛素抵抗有有益的影响。假手术(sham)或卵巢切除术(OVX)后3周,将切除卵巢的Sprague-Dawley大鼠喂食含有0 (OVX组)或0.1%染料木黄酮的饮食4周。给假大鼠喂食含有0%染料木黄酮的高脂饲料,作为对照组(假手术组)。去卵巢大鼠体重增加,胰岛素抵抗指数升高,染料木素降低胰岛素抵抗指数和肝脂肪酸合成酶活性。染料木素还与大鼠脂肪组织中琥珀酸脱氢酶和亚麻碱棕榈酰基转移酶活性的增加以及β -氧化率有关。给予染料木素的去卵巢大鼠脂肪细胞体积较小。利用微阵列数据的基因集富集分析(GSEA),我们发现OVX差异表达脂肪酸代谢、胰岛素抵抗和氧化应激的一些基因集,并被染料木黄酮逆转。这种系统的GSEA方法能够识别OVX和染料木素补充引起的基因表达变化和表型变化之间的共识。染料木素治疗可以通过改善ovx诱导的代谢功能障碍来帮助降低胰岛素抵抗,GSEA方法可能有助于提出与胰岛素抵抗相关的推定靶点。(C) 2012爱思唯尔公司版权所有。
Postmenopausal women are at higher risk for obesity and insulin resistance due to the decline of estrogen, but genistein, a phytoestrogen, may reduce the risks of these diet-related diseases. In this study, we hypothesized that supplemental genistein has beneficial effects on insulin resistance in an ovariectomized rat model by modulating lipid metabolism. Three weeks after a sham surgery (sham) or an ovariectomy (OVX), ovariectomized Sprague-Dawley rats were placed on a diet containing 0 (OVX group) or 0.1% genistein for 4 weeks. The sham rats were fed a high-fat diet containing 0% genistein and served as the control group (sham group). The ovariectomized rats showed increases in body weight and insulin resistance index, but genistein reduced insulin resistance index and the activity of hepatic fatty acid synthetase. Genistein was also associated with increased activity of succinate dehydrogenase and camitine palmitoyltransferase and the rate of beta-oxidation in the fat tissue of rats. The ovariectomized rats given genistein had smaller-sized adipocytes. Using gene-set enrichment analysis (GSEA) of microarray data, we found that a number of gene sets of fatty acid metabolism, insulin resistance, and oxidative stress were differentially expressed by OVX and reversed by genistein. This systemic approach of GSEA enables the identification of such consensus between the gene expression changes and phenotypic changes caused by OVX and genistein supplementation. Genistein treatment could help reduce insulin resistance through the amelioration of OVX-induced metabolic dysfunction, and the GSEA approach may be useful in proposing putative targets related to insulin resistance. (C) 2012 Elsevier Inc. All rights reserved.