Body composition changes and inhibition of fat development in vivo implicates androgen in regulation of stem cell lineage allocation.
Body composition changes and inhibition of fat development in vivo implicates androgen in regulation of stem cell lineage allocation.
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DOI：
10.1002/jcb.23098
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发表时间：
2011-07
影响因子：
4
通讯作者：
Wiren, Kristine M.
中科院分区：
文献类型：
--
作者：
Semirale, Anthony A.;Zhang, Xiao-Wei;Wiren, Kristine M.
雄激素调节年轻人的身体组成，随着年龄的增长而出现的睾丸激素下降与肌肉萎缩、脂肪量增加和骨质减少有关。建立了在间充质干细胞（MSC）中靶向雄激素受体（AR）过表达的转基因小鼠，以探讨雄激素信号转导在体成分调节中的作用。转基因的雄性，而不是雌性，更短，体重和内脏脂肪积累减少。双能X线吸收测定法（DXA）显示脂肪量显着减少，而瘦体重则相应增加，但观察到摄食量或运动活动无差异。棕色脂肪中的脂肪组织重量正常，但性腺和肾周贮库中的脂肪组织重量均减少，在内脏和皮下白色脂肪组织中观察到增生减少，脂肪细胞尺寸较小。虽然血清瘦素，脂联素，甘油三酯和胰岛素水平没有不同的基因型，腹膜内葡萄糖耐量试验表明，改善葡萄糖清除转基因男性。在MSC中检测到高水平的AR转基因，但在成熟脂肪组织中未检测到。减少的成纤维细胞集落形成单位表明体内骨髓中驻留的祖细胞较少。与对照组相比，在转基因小鼠的增殖前体培养物中观察到GLUT 4、PPARγ和C/EBPα的过早表达。在更成熟的培养物中，基因型之间几乎没有差异。我们提出了一种机制，其中增强的雄激素敏感性可以改变体内谱系定型，以减少祖细胞数量和脂肪发育，同时增加关键因子的表达，以促进更小的脂肪细胞，改善葡萄糖清除。
Androgens regulate body composition in youth and declining testosterone that occurs with aging is associated with muscle wasting, increased fat mass and osteopenia. Transgenic mice with targeted androgen receptor (AR) overexpression in mesenchymal stem cells (MSC) were generated to explore the role of androgen signaling in the regulation of body composition. Transgenic males, but not females, were shorter and have reduced body weight and visceral fat accumulation. Dual energy x-ray absorptiometry (DXA) revealed significant reductions in fat mass with a reciprocal increase in lean mass, yet no difference in food consumption or locomotor activity was observed. Adipose tissue weight was normal in brown fat but reduced in both gonadal and perirenal depots, and reduced hyperplasia was observed with smaller adipocyte size in visceral and subcutaneous white adipose tissue. Although serum leptin, adiponectin, triglyceride, and insulin levels were no different between the genotypes, intraperitoneal glucose tolerance testing showed improved glucose clearance in transgenic males. High levels of the AR transgene are detected in MSCs but not in mature fat tissue. Reduced fibroblast colony forming units indicate fewer progenitor cells resident in the marrow in vivo. Precocious expression of GLUT4, PPARγ and C/EBPα was observed in proliferating precursor cultures from transgenic mice compared to controls. In more mature cultures, there was little difference between the genotypes. We propose a mechanism where enhanced androgen sensitivity can alter lineage commitment in vivo to reduce progenitor number and fat development, while increasing the expression of key factors to promote smaller adipocytes with improved glucose clearance.
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影响因子：
5.8
作者：
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通讯作者：
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影响因子：
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DOI：
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作者：
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