PMID- 23707571
OWN - NLM
STAT- MEDLINE
DCOM- 20140211
LR  - 20211021
IS  - 1878-5867 (Electronic)
IS  - 0039-128X (Print)
IS  - 0039-128X (Linking)
VI  - 78
IP  - 9
DP  - 2013 Sep
TI  - Androgens inhibit adipogenesis during human adipose stem cell commitment to 
      preadipocyte formation.
PG  - 920-6
LID - S0039-128X(13)00101-3 [pii]
LID - 10.1016/j.steroids.2013.05.001 [doi]
AB  - 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 0.5-14days in the 
      presence of testosterone (T, 0-100nM) or dihydrotestosterone (DHT, 0-50nM). 
      Adipogenesis was determined by immunofluorescence microscopy and by 
      quantification of adipogenically relevant transcriptional factors, PPARgamma, C/EBPalpha 
      and C/EBPbeta. We found that a 3-day exposure of hASCs to T (50nM) or DHT (5nM) in 
      adipogenesis-inducing medium impaired lipid acquisition and decreased PPARgamma, 
      C/EBPalpha and C/EBPbeta gene expression. The inhibitory effects of T and DHT at this 
      early-stage of adipocyte differentiation, were partially and completely reversed 
      by flutamide (F, 100nM), respectively. The effect of androgens on hASC commitment 
      to a preadipocyte phenotype was examined via activation of Bone Morphogenic 
      Protein 4 (BMP4) signaling. T (50nM) and DHT (5nM) significantly inhibited the 
      stimulatory effect of BMP4-induced ASC commitment to the preadipocyte phenotype, 
      as regards PPARgamma and C/EBPalpha 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.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Chazenbalk, Gregorio
AU  - Chazenbalk G
AD  - Department of Obstetrics and Gynecology, David Geffen School of Medicine at UCLA, 
      Los Angeles, CA, United States. gchazenbalk@mednet.ucla.edu
FAU - Singh, Prapti
AU  - Singh P
FAU - Irge, Dana
AU  - Irge D
FAU - Shah, Amy
AU  - Shah A
FAU - Abbott, David H
AU  - Abbott DH
FAU - Dumesic, Daniel A
AU  - Dumesic DA
LA  - eng
GR  - P50 HD071836/HD/NICHD NIH HHS/United States
GR  - U54 HD071836/HD/NICHD NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
DEP - 20130523
PL  - United States
TA  - Steroids
JT  - Steroids
JID - 0404536
RN  - 0 (Androgen Antagonists)
RN  - 0 (Androgens)
RN  - 0 (BMP4 protein, human)
RN  - 0 (Bone Morphogenetic Protein 4)
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (CEBPA protein, human)
RN  - 0 (CEBPB protein, human)
RN  - 0 (PPAR gamma)
RN  - 0 (Receptors, Androgen)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 3XMK78S47O (Testosterone)
RN  - 76W6J0943E (Flutamide)
SB  - IM
MH  - Adipocytes/*metabolism
MH  - *Adipogenesis
MH  - Adult Stem Cells/*physiology
MH  - Androgen Antagonists/pharmacology
MH  - Androgens/pharmacology/*physiology
MH  - Bone Morphogenetic Protein 4/metabolism
MH  - CCAAT-Enhancer-Binding Protein-beta/genetics/metabolism
MH  - CCAAT-Enhancer-Binding Proteins/genetics/metabolism
MH  - Cells, Cultured
MH  - Dihydrotestosterone/*pharmacology
MH  - Female
MH  - Flutamide/pharmacology
MH  - Gene Expression
MH  - Humans
MH  - Lipid Metabolism
MH  - PPAR gamma/genetics/metabolism
MH  - Receptors, Androgen/metabolism
MH  - Signal Transduction
MH  - Testosterone/pharmacology/*physiology
PMC - PMC3951890
MID - NIHMS484875
OTO - NOTNLM
OT  - Adipogenesis
OT  - Cell commitment
OT  - Dihydrotestosterone
OT  - Testosterone
EDAT- 2013/05/28 06:00
MHDA- 2014/02/12 06:00
PMCR- 2014/09/01
CRDT- 2013/05/28 06:00
PHST- 2012/10/17 00:00 [received]
PHST- 2013/03/29 00:00 [revised]
PHST- 2013/05/06 00:00 [accepted]
PHST- 2013/05/28 06:00 [entrez]
PHST- 2013/05/28 06:00 [pubmed]
PHST- 2014/02/12 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - S0039-128X(13)00101-3 [pii]
AID - 10.1016/j.steroids.2013.05.001 [doi]
PST - ppublish
SO  - Steroids. 2013 Sep;78(9):920-6. doi: 10.1016/j.steroids.2013.05.001. Epub 2013 
      May 23.