Androgens inhibit adipogenesis during human adipose stem cell commitment to preadipocyte formation.
Androgens inhibit adipogenesis during human adipose stem cell commitment to preadipocyte formation.
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DOI：
10.1016/j.steroids.2013.05.001
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发表时间：
2013-09
期刊：
影响因子：
2.7
通讯作者：
Dumesic DA
中科院分区：
文献类型：
--
作者：
Chazenbalk G;Singh P;Irge D;Shah A;Abbott DH;Dumesic DA
雄激素在调节体脂分布中起着关键作用。脂肪生成是指多能脂肪干细胞（ASC）在分化为脂肪细胞之前首先成为前脂肪细胞（ASC向前脂肪细胞的定型）的过程。雄激素抑制两种性别的人（h）皮下（SC）腹部前脂肪细胞分化，但其对hASC前脂肪细胞形成的影响尚不清楚。因此，我们研究了雄激素暴露于从非肥胖女性的SC腹部脂肪中分离的人（h）ASC是否会损害其对前脂肪细胞形成和/或随后分化为脂肪细胞的承诺。为此，在睾酮（T，0-100 nM）或二氢睾酮（DHT，0-50 nM）存在下，将来自SC腹部脂肪抽吸物的分离的hASC在脂肪生成诱导培养基中培养0.5-14天。通过免疫荧光显微镜和定量脂肪生成相关转录因子PPARγ、C/EBPα和C/EBPβ来确定脂肪生成。我们发现，在脂肪生成诱导培养基中，将hASC暴露于T（50 nM）或DHT（5 nM）3天会损害脂质获得，并降低PPARγ、C/EBPα和C/EBPβ基因表达。氟他胺（F，100 nM）分别部分和完全逆转了T和DHT在脂肪细胞分化早期阶段的抑制作用。雄激素对hASC向前脂肪细胞表型定型的作用通过激活BMP 4信号传导来检查。T（50 nM）和DHT（5 nM）显著抑制BMP 4诱导的ASC向前脂肪细胞表型定型的刺激作用，就PPARγ和C/EBPα基因表达而言。我们的研究结果表明，雄激素，部分通过雄激素受体的作用，损害BMP 4诱导的承诺SC hASC的前脂肪细胞，也减少早期脂肪细胞分化，可能限制脂肪细胞的数量和脂肪储存在SC腹部脂肪。
Androgens play a pivotal role in the regulation of body fat distribution. Adipogenesis is a process whereby multipotent adipose stem cells (ASCs) initially become preadipocytes (ASC commitment to preadipocytes) before differentiating into adipocytes. Androgens inhibit human (h) subcutaneous (SC) abdominal preadipocyte differentiation in both sexes, but their effects on hASC commitment to preadipocyte formation is unknown. We therefore examined whether androgen exposure to human (h) ASCs, isolated from SC abdominal adipose of nonobese women, impairs their commitment to preadipocyte formation and/or subsequent differentiation into adipocytes. For this, isolated hASCs from SC abdominal lipoaspirate were cultured in adipogenesis-inducing medium for 0.5–14 days in the presence of testosterone (T, 0–100 nM) or dihydrotestosterone (DHT, 0–50 nM). Adipogenesis was determined by immunofluorescence microscopy and by quantification of adipogenically relevant transcriptional factors, PPARγ, C/EBPα and C/EBPβ. We found that a 3-day exposure of hASCs to T (50 nM) or DHT (5 nM) in adipogenesis-inducing medium impaired lipid acquisition and decreased PPARγ, C/EBPα and C/EBPβ gene expression. The inhibitory effects of T and DHT at this early-stage of adipocyte differentiation, were partially and completely reversed by flutamide (F, 100 nM), respectively. The effect of androgens on hASC commitment to a preadipocyte phenotype was examined via activation of BMP4 signaling. T (50 nM) and DHT (5nM) significantly inhibited the stimulatory effect of BMP4-induced ASC commitment to the preadipocyte phenotype, as regards PPARγ and C/EBPα gene expression. Our findings indicate that androgens, in part through androgen receptor action, impair BMP4-induced commitment of SC hASCs to preadipocytes and also reduce early-stage adipocyte differentiation, perhaps limiting adipocyte numbers and fat storage in SC abdominal adipose.
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影响因子：
3.7
作者：
Baglioni S;Cantini G;Poli G;Francalanci M;Squecco R;Di Franco A;Borgogni E;Frontera S;Nesi G;Liotta F;Lucchese M;Perigli G;Francini F;Forti G;Serio M;Luconi M
通讯作者：
Luconi M
DOI：
10.1007/s12265-009-9101-1
发表时间：
2009-09-01
影响因子：
3.4
作者：
Nedungadi, Thekkethil P.;Clegg, Deborah J.
通讯作者：
Clegg, Deborah J.
影响因子：
3.6
作者：
Moseley, Timothy A.;Zhu, Min;Hedrick, Marc H.
通讯作者：
Hedrick, Marc H.
影响因子：
5.8
作者：
McCartney, Christopher R.;Blank, Susan K.;Marshall, John C.
通讯作者：
Marshall, John C.
影响因子：
7.7
作者：
Nishimura, Satoshi;Manabe, Ichiro;Sugiura, Seiryo
通讯作者：
Sugiura, Seiryo