Diet, gonadal sex, and sex chromosome complement influence white adipose tissue miRNA expression.
Diet, gonadal sex, and sex chromosome complement influence white adipose tissue miRNA expression.
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DOI：
10.1186/s12864-017-3484-1
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发表时间：
2017-01-17
期刊：
影响因子：
4.4
通讯作者：
Reue K
中科院分区：
文献类型：
--
作者：
Link JC;Hasin-Brumshtein Y;Cantor RM;Chen X;Arnold AP;Lusis AJ;Reue K
microRNA（miRNAs）是一种非编码RNA小分子，通过靶向特定的mRNA种类降解或干扰翻译来调控基因表达。特异性miRNA是脂肪形成的关键调节因子，并且在瘦小鼠和肥胖小鼠的脂肪组织中以不同水平表达。男性和女性的白色脂肪组织的脂质积累和分布程度不同，目前尚不清楚脂肪组织特异性miRNA表达的性别差异是否可能导致这种二型性。通常，性别差异归因于卵巢或睾丸分泌的激素。然而，性染色体补体（XX与XY）也是性别差异的决定因素，并可能调节脂肪细胞中的miRNA表达。为了确定脂肪组织miRNA表达的性别差异并了解潜在的机制，我们在四个核心基因型小鼠模型的性腺脂肪库中进行了高通量miRNA测序。该模型由XX雌性、XX雄性、XY雌性和XY雄性小鼠组成，使我们能够评估性腺类型（雄性与雌性）和性染色体补体（XX与XY）对miRNA表达谱的独立影响。我们还评估了高脂肪饮食对脂肪组织miRNA谱性别差异的影响。我们确定了一个男性-女性的整体miRNA表达谱的影响，在喂食饲料的小鼠，与女性相比，男性性腺脂肪组织中的表达更高的偏见。这种性别偏见在性腺切除术后消失，表明性腺分泌物的循环水平调节miRNA表达谱。在高脂饮食16周后，miRNA表达分布在XY脂肪组织中的表达高于XX脂肪组织。主成分分析显示，高脂肪饮食对miRNA谱变异有显著影响，而性腺分泌物和性染色体补体的影响较小。我们的研究结果表明，脂肪组织中的总体miRNA表达谱受性腺激素和性染色体补体的影响，并且表达谱响应于性腺切除术和高脂肪饮食而改变。差异miRNA表达谱可能导致脂肪组织基因表达、脂肪组织发育和饮食诱导的肥胖的性别差异。本文的在线版本（doi：10.1186/s12864-017-3484-1）包含补充材料，可供授权用户使用。
MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by targeting specific mRNA species for degradation or interfering with translation. Specific miRNAs are key regulators of adipogenesis, and are expressed at different levels in adipose tissue from lean and obese mice. The degree of lipid accumulation and distribution of white adipose tissue differs between males and females, and it is unknown whether sex differences in adipose tissue-specific miRNA expression may contribute to this dimorphism. Typically, sex differences are attributed to hormones secreted from ovaries or testes. However, the sex chromosome complement (XX versus XY) is also a determinant of sex differences and may regulate miRNA expression in adipocytes. To identify sex differences in adipose tissue miRNA expression and to understand the underlying mechanisms, we performed high-throughput miRNA sequencing in gonadal fat depots of the Four Core Genotypes mouse model. This model, which consists of XX female, XX male, XY female, and XY male mice, allowed us to assess independent effects of gonadal type (male vs. female) and sex chromosome complement (XX vs. XY) on miRNA expression profiles. We have also assessed the effects of a high fat diet on sex differences in adipose tissue miRNA profiles. We identified a male–female effect on the overall miRNA expression profile in mice fed a chow diet, with a bias toward higher expression in male compared to female gonadal adipose tissue. This sex bias disappeared after gonadectomy, suggesting that circulating levels of gonadal secretions modulate the miRNA expression profile. After 16 weeks of high fat diet, the miRNA expression distribution was shifted toward higher expression in XY vs. XX adipose tissue. Principal component analysis revealed that high fat diet has a substantial effect on miRNA profile variance, while gonadal secretions and sex chromosome complement each have milder effects. Our results demonstrate that the overall miRNA expression profile in adipose tissue is influenced by gonadal hormones and the sex chromosome complement, and that expression profiles change in response to gonadectomy and high fat diet. Differential miRNA expression profiles may contribute to sex differences in adipose tissue gene expression, adipose tissue development, and diet-induced obesity. The online version of this article (doi:10.1186/s12864-017-3484-1) contains supplementary material, which is available to authorized users.