Increased death of adipose cells, a path to release cell-free DNA into systemic circulation of obese women.
Increased death of adipose cells, a path to release cell-free DNA into systemic circulation of obese women.
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DOI：
10.1038/oby.2012.138
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发表时间：
2012-11
期刊：
影响因子：
6.9
通讯作者：
Hauguel-de Mouzon, Sylvie
中科院分区：
文献类型：
--
作者：
Haghiac, Maricela;Vora, Neeta L.;Basu, Subhabrata;Johnson, Kirby L.;Presley, Larraine;Bianchi, Diana W.;Hauguel-de Mouzon, Sylvie
脂肪组织的重塑需要支持脂肪量的扩张。在肥胖症中，脂肪细胞死亡的增加有助于细胞更新的加速。我们已经证明，妊娠期肥胖与脂肪组织的代谢和免疫改变有关。在这项研究中，我们描述了肥胖孕妇脂肪细胞死亡增加的机制及其功能后果。我们假设肥胖女性白色脂肪组织中死细胞的更新率较高，这将转化为无细胞 DNA (cfDNA) 释放到她们的体循环中。与瘦女性相比，肥胖女性的脂肪量增加是由于肥大脂肪细胞数量较少以及基质血管部分（SVF）中巨噬细胞的积累所致。肥胖者的脂肪细胞显示出增强的坏死，质膜上的周脂质染色丧失。与瘦人相比，肥胖的 SVF 细胞凋亡显着，caspase 9 和 caspase 3 的表达增加，TUNEL 阳性 CD68 巨噬细胞的比例更高。尽管胎儿循环 cfDNA 浓度没有变化，但肥胖女性的循环 GAPDH cfDNA 和脂肪组织 GAPDH mRNA 增加了 2 倍。母体全身 GAPDH cfDNA 与 BMI 和妊娠体重增加呈正相关。这些数据表明，肥胖孕妇脂肪组织的主动重塑导致母体来源的 cfDNA 释放到循环中的增加。
Remodeling of adipose tissue is required to support the expansion of adipose mass. In obesity, an increased death of adipocytes contributes to the accelerated cellular turnover. We have shown that obesity in pregnancy is associated with metabolic and immune alterations in the adipose tissue. In this study we characterized the mechanisms responsible for increased death of adipose cells of pregnant obese women and its functional consequences. We postulated that a higher turnover of dead cells in white adipose tissue of obese women would translate into release of cell free DNA (cfDNA) into their systemic circulation. Increase in adipose mass of obese compared to lean women results from a lesser number of hypertrophic adipocytes and an accumulation of macrophages in the stromal vascular fraction (SVF). The adipocytes of obese displayed enhanced necrosis with a loss of perilipin staining at the plasma membrane. Apoptosis was prominent in SVF cells with an increased expression of caspase 9 and caspase 3 and a higher rate of TUNEL positive CD68 macrophages in obese vs lean. Whereas circulating fetal cfDNA concentrations were not changed, there was a 2-fold increase in circulating GAPDH cfDNA and adipose tissue GAPDH mRNA in obese women. The maternal systemic GAPDH cfDNA was positively correlated with BMI and gestational weight gain. These data suggest that the active remodeling of adipose tissue of obese pregnant women results in an increased release of cfDNA of maternal origin into the circulation.
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影响因子：
2.9
作者：
Lemmens, HJM;Bernstein, DP;Brodsky, JB
通讯作者：
Brodsky, JB
DOI：
10.1016/s0002-9378(03)00828-7
发表时间：
2003-12-01
影响因子：
9.8
作者：
Catalano, PM;Thomas, A;Amini, SB
通讯作者：
Amini, SB
影响因子：
7.7
作者：
Nishimura, Satoshi;Manabe, Ichiro;Sugiura, Seiryo
通讯作者：
Sugiura, Seiryo
DOI：
10.1152/ajpendo.90296.2008
发表时间：
2008-08-01
影响因子：
5.1
作者：
Pang, Can;Gao, Zhanguo;Ye, Jianping
通讯作者：
Ye, Jianping
影响因子：
6.2
作者：
Kamat, Aparna A.;Baldwin, Mathew;Urbauer, Diana;Dang, Diana;Han, Liz Y.;Godwin, Andrew;Karlan, Beth Y.;Simpson, Joe L.;Gershenson, David M.;Coleman, Robert L.;Bischoff, Farideh Z.;Sood, Anil K.
通讯作者：
Sood, Anil K.