Sex-dimorphism in Cardiac Nutrigenomics: effect of Trans fat and/or Monosodium Glutamate consumption
Sex-dimorphism in Cardiac Nutrigenomics: effect of Trans fat and/or Monosodium Glutamate consumption
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DOI：
10.1186/1471-2164-12-555
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发表时间：
2011-11-12
期刊：
影响因子：
4.4
通讯作者：
Al-Mohanna, Futwan A.
中科院分区：
文献类型：
--
作者：
Collison, Kate S.;Zaidi, Marya Z.;Al-Mohanna, Futwan A.
背景：缺乏关于饮食对心脏基因表达的生物学性别差异的信息，这促使了目前的营养基因组学研究。性二型性存在于对饮食的生理和转录反应中，特别是对高脂肪饮食的反应。反式脂肪酸(TFA)的摄入与心脏病风险的显著增加有关，在心脏病中，性别二型性明显，男性患病率更高。在新生儿期暴露于谷氨酸单钠(MSG)的动物中已注意到心血管系统的损害，先前已注意到MSG处理的动物生长轴中的性别二型性。加工食品可能同时含有TFA和MSG。方法：与对照饮食相比，我们研究了摄入TFA和/或味精的雄性和雌性C57BL/6J小鼠的生理差异和基因表达的变化。结果：喂食TFA的小鼠心脏和体重百分比增加更大，他们也表现出血脂异常(P<；0.05)。喂食味精的雌性大鼠的心脏比雄性小(P<；0.05)。2因素方差分析表明，三氟化钠饮食诱导的男性心脏差异表达基因(DEG)是女性的两倍多(P<；0.001)；包括GATA4、MEF2d和Srebf2在内的男性差异表达基因下调的数量是女性的4倍。功能基因本体论(GO)类别的丰富与转录、磷酸化和解剖结构相关(P<；0.01)。一些基因在男性中上调，在女性中下调，包括促凋亡的组蛋白脱乙酰酶-2(HDAC2)。在喂食味精的动物的心脏转录中也观察到了性别二型性，性别上调了大约100度，在GO类别中表现出性别特异性的差异。对所有饮食组合之间心脏基因表达的比较发现，111个转录子仅在男性中显著，仅在女性中显著，74个转录本被鉴定为对饮食操纵的反应在两性中存在差异。结论：我们的模型发现，与对照组相比，服用三氟乙酸和/或味精的小鼠心脏转录谱发生了重大变化，这反映在4个饮食组的生理谱显著不同。心脏转录中性二型性的鉴定可能会为将来的性别特异性药物提供基础。
Background: A paucity of information on biological sex-specific differences in cardiac gene expression in response to diet has prompted this present nutrigenomics investigation. Sexual dimorphism exists in the physiological and transcriptional response to diet, particularly in response to high-fat feeding. Consumption of Trans-fatty acids (TFA) has been linked to substantially increased risk of heart disease, in which sexual dimorphism is apparent, with males suffering a higher disease rate. Impairment of the cardiovascular system has been noted in animals exposed to Monosodium Glutamate (MSG) during the neonatal period, and sexual dimorphism in the growth axis of MSG-treated animals has previously been noted. Processed foods may contain both TFA and MSG.Methods: We examined physiological differences and changes in gene expression in response to TFA and/or MSG consumption compared to a control diet, in male and female C57BL/6J mice.Results: Heart and % body weight increases were greater in TFA-fed mice, who also exhibited dyslipidemia (P < 0.05). Hearts from MSG-fed females weighed less than males (P < 0.05). 2-factor ANOVA indicated that the TFA diet induced over twice as many cardiac differentially expressed genes (DEGs) in males compared to females (P < 0.001); and 4 times as many male DEGs were downregulated including Gata4, Mef2d and Srebf2. Enrichment of functional Gene Ontology (GO) categories were related to transcription, phosphorylation and anatomic structure (P < 0.01). A number of genes were upregulated in males and downregulated in females, including pro-apoptotic histone deacetylase-2 (HDAC2). Sexual dimorphism was also observed in cardiac transcription from MSG-fed animals, with both sexes upregulating approximately 100 DEGs exhibiting sex-specific differences in GO categories. A comparison of cardiac gene expression between all diet combinations together identified a subset of 111 DEGs significant only in males, 64 DEGs significant in females only, and 74 transcripts identified as differentially expressed in response to dietary manipulation in both sexes.Conclusion: Our model identified major changes in the cardiac transcriptional profile of TFA and/or MSG-fed mice compared to controls, which was reflected by significant differences in the physiological profile within the 4 diet groups. Identification of sexual dimorphism in cardiac transcription may provide the basis for sex-specific medicine in the future.