Stem cell activation in adults can reverse detrimental changes in body composition to reduce fat and increase lean mass in both sexes.
Stem cell activation in adults can reverse detrimental changes in body composition to reduce fat and increase lean mass in both sexes.
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DOI：
10.1002/jcb.23288
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发表时间：
2011-12
影响因子：
4
通讯作者：
Zhang, Xiao-Wei
中科院分区：
文献类型：
--
作者：
Wiren, Kristine M.;Hashimoto, Joel G.;Zhang, Xiao-Wei
身体成分的有害变化通常与睾酮水平下降有关。在这里，我们评估了这样一个概念：产生脂肪和肌肉组织的多能间充质干细胞（MSC）可以在改变成人现有的身体成分方面发挥重要作用。采用干细胞中靶向雄激素受体（AR）过度表达的转基因小鼠。对野生型同窝小鼠和 AR 转基因雄性和雌性小鼠进行性腺切除，并在 2 个月内不进行治疗。性腺机能减退期结束后，小鼠接受 5α-二氢睾酮 (DHT) 治疗 6 周。睾丸切除术（ORX）后，与假手术相比，野生型雄性的瘦肉质量减少，脂肪质量增加。 DHT治疗有利于部分恢复身体成分。在野生型雌性中，卵巢切除术 (OVX) 产生了类似的变化，但 DHT 没有改善。在靶向 AR 转基因小鼠中，DHT 治疗使瘦肉量增加，脂肪量减少至假手术水平。与野生型雌性小鼠相比，雌性转基因小鼠的 DHT 治疗显着改善了 OVX 后导致的脂肪增加和瘦肉质量变化。我们的结果表明，DHT 给药可减少野生型雄性而非雌性的脂肪量并增加瘦体重，这表明野生型雌性对雄激素治疗不那么敏感。由于雄性和雌性转基因小鼠都比野生型小鼠反应更灵敏，因此结果表明，身体成分仍然与成体干细胞的命运相关，并且干细胞中的靶向雄激素信号传导可以在逆转两性身体成分的有害变化方面发挥重要作用。
Detrimental changes in body composition are often associated with declining levels of testosterone. Here we evaluated the notion that multipotent mesenchymal stem cells (MSC), that give rise to both fat and muscle tissue, can play a significant role to alter existing body composition in the adult. Transgenic mice with targeted androgen receptor (AR) overexpression in stem cells were employed. Wild-type littermate and AR-transgenic male and female mice were gonadectomized and left untreated for 2 months. After the hypogonadal period, mice were then treated with 5α-dihydrotestosterone (DHT) for 6 weeks. After orchidectomy (ORX), wild-type males have reduced lean mass and increased fat mass compared to shams. DHT treatment was beneficial to partially restore body composition. In wild-type females, ovariectomy (OVX) produced a similar change but there was no improvement with DHT. In targeted AR transgenic mice, DHT treatment increased lean and reduced fat mass to sham levels. In contrast to wild-type females, DHT treatment in female transgenic mice significantly ameliorated the increased fat and decreased lean mass changes that result after OVX. Our results indicate that DHT administration reduces fat mass and increases lean mass in wild-type males but not females, indicating that wild-type females are not as sensitive to androgen treatment. Because both male and female transgenic mice are more responsive than wild-type, results suggest that body composition remains linked to stem cell fate in the adult and that targeted androgen signaling in stem cells can play a significant role to reverse detrimental changes in body composition in both sexes.
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影响因子：
24
作者：
Hare, Joshua M.;Traverse, Jay H.;Henry, Timothy D.;Dib, Nabil;Strumpf, Robert K.;Schulman, Steven P.;Gerstenblith, Gary;DeMaria, Anthony N.;Denktas, Ali E.;Gammon, Roger S.;Hermiller, James B., Jr.;Reisman, Mark A.;Schaer, Gary L.;Sherman, Warren
通讯作者：
Sherman, Warren
影响因子：
20.1
作者：
Hatzistergos KE;Quevedo H;Oskouei BN;Hu Q;Feigenbaum GS;Margitich IS;Mazhari R;Boyle AJ;Zambrano JP;Rodriguez JE;Dulce R;Pattany PM;Valdes D;Revilla C;Heldman AW;McNiece I;Hare JM
通讯作者：
Hare JM
影响因子：
2.3
作者：
Dati, E.;Baroncelli, G. I.;Bertelloni, S.
通讯作者：
Bertelloni, S.
DOI：
10.1016/j.jsbmb.2007.09.001
发表时间：
2008-02-01
影响因子：
4.1
作者：
Blouin, Karine;Boivin, Ariane;Tchernof, Andre
通讯作者：
Tchernof, Andre
影响因子：
4.9
作者：
Gruber, DM;Sator, MO;Huber, JC
通讯作者：
Huber, JC