PMID- 25304490
OWN - NLM
STAT- MEDLINE
DCOM- 20150804
LR  - 20211021
IS  - 1879-3177 (Electronic)
IS  - 0887-2333 (Print)
IS  - 0887-2333 (Linking)
VI  - 29
IP  - 1
DP  - 2015 Feb
TI  - PCB126 inhibits adipogenesis of human preadipocytes.
PG  - 132-41
LID - S0887-2333(14)00188-X [pii]
LID - 10.1016/j.tiv.2014.09.015 [doi]
AB  - Emerging evidence indicates that persistent organic pollutants (POPs), including 
      polychlorinated biphenyls (PCBs), are involved in the development of diabetes. 
      Dysfunctional adipocytes play a significant role in initiating insulin 
      resistance. Preadipocytes make up a large portion of adipose tissue and are 
      necessary for the generation of functional mature adipocytes through 
      adipogenesis. PCB126 is a dioxin-like PCB and a potent aryl hydrocarbon receptor 
      (AhR) agonist. We hypothesized that PCB126 may be involved in the development of 
      diabetes through disruption of adipogenesis. Using a newly developed human 
      preadipocyte cell line called NPAD (Normal PreADipocytes), we found that exposure 
      of preadipocytes to PCB126 resulted in significant reduction in their subsequent 
      ability to fully differentiate into adipocytes, more so than when the cells were 
      exposed to PCB126 during differentiation. Reduction in differentiation by PCB126 
      was associated with downregulation of transcript levels of a key adipocyte 
      transcription factor, PPARgamma, and late adipocyte differentiation genes. An AhR 
      antagonist, CH223191, blocked this effect. These studies indicate that 
      preadipocytes are particularly sensitive to the effects of PCB126 and suggest 
      that AhR activation inhibits PPARgamma transcription and subsequent adipogenesis. Our 
      results validate the NPAD cell line as a useful model for studying the effects of 
      POPs on adipogenesis.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Gadupudi, Gopi
AU  - Gadupudi G
AD  - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, 
      Iowa City, IA 52242, United States; Department of Occupational & Environmental 
      Health, The University of Iowa, Iowa City, IA 52242, United States.
FAU - Gourronc, Francoise A
AU  - Gourronc FA
AD  - Department of Microbiology, The University of Iowa, Iowa City, IA 52242, United 
      States.
FAU - Ludewig, Gabriele
AU  - Ludewig G
AD  - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, 
      Iowa City, IA 52242, United States; Department of Occupational & Environmental 
      Health, The University of Iowa, Iowa City, IA 52242, United States.
FAU - Robertson, Larry W
AU  - Robertson LW
AD  - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, 
      Iowa City, IA 52242, United States; Department of Occupational & Environmental 
      Health, The University of Iowa, Iowa City, IA 52242, United States.
FAU - Klingelhutz, Aloysius J
AU  - Klingelhutz AJ
AD  - Department of Microbiology, The University of Iowa, Iowa City, IA 52242, United 
      States. Electronic address: al-klingelhutz@uiowa.edu.
LA  - eng
GR  - P30 ES005605/ES/NIEHS NIH HHS/United States
GR  - P42 ES013661/ES/NIEHS NIH HHS/United States
GR  - P30 ES05605/ES/NIEHS NIH HHS/United States
GR  - P42 ES 013661/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20141007
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (PPAR gamma)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - TSH69IA9XF (3,4,5,3',4'-pentachlorobiphenyl)
SB  - IM
MH  - Adipocytes/*drug effects
MH  - Adipogenesis/*drug effects
MH  - Cell Differentiation/drug effects
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cytochrome P-450 CYP1A1/drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Flow Cytometry
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - PPAR gamma/antagonists & inhibitors
MH  - Polychlorinated Biphenyls/*toxicity
MH  - Reverse Transcriptase Polymerase Chain Reaction
PMC - PMC4250299
MID - NIHMS638572
OTO - NOTNLM
OT  - Adipocytes
OT  - AhR
OT  - Diabetes
OT  - PCBs
OT  - PPARgamma
OT  - Preadipocytes
EDAT- 2014/10/12 06:00
MHDA- 2015/08/05 06:00
PMCR- 2016/02/01
CRDT- 2014/10/12 06:00
PHST- 2014/06/29 00:00 [received]
PHST- 2014/08/28 00:00 [revised]
PHST- 2014/09/25 00:00 [accepted]
PHST- 2014/10/12 06:00 [entrez]
PHST- 2014/10/12 06:00 [pubmed]
PHST- 2015/08/05 06:00 [medline]
PHST- 2016/02/01 00:00 [pmc-release]
AID - S0887-2333(14)00188-X [pii]
AID - 10.1016/j.tiv.2014.09.015 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2015 Feb;29(1):132-41. doi: 10.1016/j.tiv.2014.09.015. Epub 
      2014 Oct 7.