一般來說,，男女兩性在體重，脂肪分布及代謝疾病上具有較大的差異,。之前的研究認(rèn)為,，這很大程度上歸咎于男性及女性體內(nèi)不同性激素的作用。
近日,，來自美國(guó)加州大學(xué)洛杉機(jī)分校的研究人員Karen Reue等人發(fā)現(xiàn),，細(xì)胞內(nèi)X染色體的數(shù)目是肥胖表現(xiàn)出性別差異的內(nèi)因。相關(guān)研究成果于5月10日發(fā)表在PLoS Genetics,。
他們使用了一個(gè)獨(dú)特的,，被稱為“four core genotypes”的老鼠模型，來區(qū)分性腺性別（睪丸或者卵巢）及性染色體(XX或者XY)的作用,。利用這種模型,，他們產(chǎn)生了性腺性別為雌性及雄性的老鼠，而且它們具有的是XX或者XY性染色體,。
為了排除性激素的作用,，揭示性染色體對(duì)肥胖的作用，他們切除了老鼠的性腺,。結(jié)果發(fā)現(xiàn),，具有XX性染色體的老鼠，不論它們是何種性腺表型,，它們均表現(xiàn)出約2倍的肥胖,，需要攝取更多的食物量。而且,，具有兩個(gè)X染色體的老鼠在高脂肪飲食環(huán)境下,，體重增加加速，具有發(fā)達(dá)的脂肪肝和提高的血脂及胰島素水平。
對(duì)性染色體為XO和XXY的老鼠,，進(jìn)一步的遺傳學(xué)研究表明,，XX及XY老鼠表型的差異可歸咎于細(xì)胞內(nèi)X染色體的數(shù)目，而不是Y染色體的數(shù)目,。
研究發(fā)現(xiàn),，一些基因能夠逃避X染色體的失活，對(duì)比于XY老鼠,，這些基因在XX老鼠的脂肪組織及肝臟內(nèi)表現(xiàn)出高表達(dá)水平,，可能因此促進(jìn)了肥胖的性別差異。Karen Reue表示,，該研究第一次闡明了性染色體數(shù)目促進(jìn)了肥胖及代謝的性別差異,。（生物谷Deepblue編譯）
doi: 10.1371/journal.pgen.1002709
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The Number of X Chromosomes Causes Sex Differences in Adiposity in Mice
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.
