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腾讯登录X染色体数目是肥胖性别差异的原因
| 导读 | 一般来说，男女两性在体重，脂肪分布及代谢疾病上具有较大的差异。之前的研究认为，这很大程度上归咎于男性及女性体内不同性激素的作用。
近日，来自美国加州大学洛杉机分校的研究人员Karen Reue等人发现，细胞内X染色体的数目是肥胖表现出性别差异的内因。相关研究成果于5月10日发表在<em>PLoS Genetics</em>。
他们使用了一个独特的，被称为“fou... |
一般来说，男女两性在体重，脂肪分布及代谢疾病上具有较大的差异。之前的研究认为，这很大程度上归咎于男性及女性体内不同性激素的作用。
近日，来自美国加州大学洛杉机分校的研究人员Karen Reue等人发现，细胞内X染色体的数目是肥胖表现出性别差异的内因。相关研究成果于5月10日发表在<em>PLoS Genetics</em>。
他们使用了一个独特的，被称为“four core genotypes”的老鼠模型，来区分性腺性别（睾丸或者卵巢）及性染色体(XX或者XY)的作用。利用这种模型，他们产生了性腺性别为雌性及雄性的老鼠，而且它们具有的是XX或者XY性染色体。
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为了排除性激素的作用，揭示性染色体对肥胖的作用，他们切除了老鼠的性腺。结果发现，具有XX性染色体的老鼠，不论它们是何种性腺表型，它们均表现出约2倍的肥胖，需要摄取更多的食物量。而且，具有两个X染色体的老鼠在高脂肪饮食环境下，体重增加加速，具有发达的脂肪肝和提高的血脂及胰岛素水平。
对性染色体为XO和XXY的老鼠，进一步的遗传学研究表明，XX及XY老鼠表型的差异可归咎于细胞内X染色体的数目，而不是Y染色体的数目。
研究发现，一些基因能够逃避X染色体的失活，对比于XY老鼠，这些基因在XX老鼠的脂肪组织及肝脏内表现出高表达水平，可能因此促进了肥胖的性别差异。Karen Reue表示，该研究第一次阐明了性染色体数目促进了肥胖及代谢的性别差异。
<br/><strong>原文摘要：</strong><br/>
<br/><strong>The Number of X Chromosomes Causes Sex Differences in Adiposity in Mice </strong><br/>
Xuqi Chen, Rebecca McClusky, Jenny Chen, Simon W. Beaven, Peter Tontonoz, Arthur P. Arnold, Karen Reue.
Sexual dimorphism in body weight, fat distribution, and metabolic disease has been attributed largely to differential effects of male and female gonadal hormones.Here, we report that the number of X chromosomes within cells also contributes to these sex differences. We employed a unique mouse model, known as the “four core genotypes,” to distinguish between effects of gonadal sex (testes or ovaries) and sex chromosomes (XX or XY). With this model, we produced gonadal male and female mice carrying XX or XY sex chromosome complements.Mice were gonadectomized to remove the acute effects of gonadal hormones and to uncover effects of sex chromosome complement on obesity. Mice with XX sex chromosomes (relative to XY), regardless of their type of gonad, had up to 2-fold increased adiposity and greater food intake during daylight hours, when mice are normally inactive.Mice with two X chromosomes also had accelerated weight gain on a high fat diet and developed fatty liver and elevated lipid and insulin levels. Further genetic studies with mice carrying XO and XXY chromosome complements revealed that the differences between XX and XY mice are attributable to dosage of the X chromosome, rather than effects of the Y chromosome.A subset of genes that escape X chromosome inactivation exhibited higher expression levels in adipose tissue and liver of XX compared to XY mice, and may contribute to the sex differences in obesity. Overall, our study is the first to identify sex chromosome complement, a factor distinguishing all male and female cells, as a cause of sex differences in obesity and metabolism.
近日，来自美国加州大学洛杉机分校的研究人员Karen Reue等人发现，细胞内X染色体的数目是肥胖表现出性别差异的内因。相关研究成果于5月10日发表在<em>PLoS Genetics</em>。
他们使用了一个独特的，被称为“four core genotypes”的老鼠模型，来区分性腺性别（睾丸或者卵巢）及性染色体(XX或者XY)的作用。利用这种模型，他们产生了性腺性别为雌性及雄性的老鼠，而且它们具有的是XX或者XY性染色体。
<!--more-->
为了排除性激素的作用，揭示性染色体对肥胖的作用，他们切除了老鼠的性腺。结果发现，具有XX性染色体的老鼠，不论它们是何种性腺表型，它们均表现出约2倍的肥胖，需要摄取更多的食物量。而且，具有两个X染色体的老鼠在高脂肪饮食环境下，体重增加加速，具有发达的脂肪肝和提高的血脂及胰岛素水平。
对性染色体为XO和XXY的老鼠，进一步的遗传学研究表明，XX及XY老鼠表型的差异可归咎于细胞内X染色体的数目，而不是Y染色体的数目。
研究发现，一些基因能够逃避X染色体的失活，对比于XY老鼠，这些基因在XX老鼠的脂肪组织及肝脏内表现出高表达水平，可能因此促进了肥胖的性别差异。Karen Reue表示，该研究第一次阐明了性染色体数目促进了肥胖及代谢的性别差异。
<br/><strong>原文摘要：</strong><br/>
<br/><strong>The Number of X Chromosomes Causes Sex Differences in Adiposity in Mice </strong><br/>
Xuqi Chen, Rebecca McClusky, Jenny Chen, Simon W. Beaven, Peter Tontonoz, Arthur P. Arnold, Karen Reue.
Sexual dimorphism in body weight, fat distribution, and metabolic disease has been attributed largely to differential effects of male and female gonadal hormones.Here, we report that the number of X chromosomes within cells also contributes to these sex differences. We employed a unique mouse model, known as the “four core genotypes,” to distinguish between effects of gonadal sex (testes or ovaries) and sex chromosomes (XX or XY). With this model, we produced gonadal male and female mice carrying XX or XY sex chromosome complements.Mice were gonadectomized to remove the acute effects of gonadal hormones and to uncover effects of sex chromosome complement on obesity. Mice with XX sex chromosomes (relative to XY), regardless of their type of gonad, had up to 2-fold increased adiposity and greater food intake during daylight hours, when mice are normally inactive.Mice with two X chromosomes also had accelerated weight gain on a high fat diet and developed fatty liver and elevated lipid and insulin levels. Further genetic studies with mice carrying XO and XXY chromosome complements revealed that the differences between XX and XY mice are attributable to dosage of the X chromosome, rather than effects of the Y chromosome.A subset of genes that escape X chromosome inactivation exhibited higher expression levels in adipose tissue and liver of XX compared to XY mice, and may contribute to the sex differences in obesity. Overall, our study is the first to identify sex chromosome complement, a factor distinguishing all male and female cells, as a cause of sex differences in obesity and metabolism.
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