PMID- 20567236
OWN - NLM
STAT- MEDLINE
DCOM- 20100929
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 90
IP  - 9
DP  - 2010 Sep
TI  - Selective deletion of adipocytes, but not preadipocytes, by TNF-alpha through 
      C/EBP- and PPARgamma-mediated suppression of NF-kappaB.
PG  - 1385-95
LID - 10.1038/labinvest.2010.118 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a key regulator of adipose tissue 
      mass, but mechanisms underlying this effect have not been fully elucidated. We 
      found that exposure to TNF-alpha caused a significant decrease in the number of 
      adipocytes, but not preadipocytes. Subsequent experiments revealed that TNF-alpha 
      selectively deleted adipocytes through induction of apoptosis. Following exposure 
      to TNF-alpha, rapid activation of nuclear factor-kappaB (NF-kappaB) was observed 
      only in preadipocytes, but not in adipocytes. Inhibition of NF-kappaB rendered 
      preadipocytes susceptible to TNF-alpha-induced apoptosis, suggesting that 
      different activity of NF-kappaB is the determinant for the distinct apoptotic 
      responses. During adipocyte differentiation, expression and activity of 
      peroxisome proliferator-activated receptor-gamma (PPARgamma) were upregulated. 
      Treatment of preadipocytes with a PPARgamma agonist attenuated NF-kappaB 
      activation and rendered the cells vulnerable to TNF-alpha-induced apoptosis. 
      Conversely, treatment of adipocytes with a PPARgamma antagonist enhanced 
      NF-kappaB activation and conferred resistance to TNF-alpha-induced apoptosis, 
      suggesting involvement of PPARgamma in the suppression of NF-kappaB in 
      adipocytes. We also found that, following differentiation, expression and 
      activity of CCAAT/enhancer binding protein (C/EBP), especially C/EBPalpha and 
      C/EBPbeta, were upregulated in adipocytes. Overexpression of individual C/EBPs 
      significantly inhibited activation of NF-kappaB in preadipocytes. Furthermore, 
      transfection with siRNA for C/EBPalpha or C/EBPbeta enhanced activity of 
      NF-kappaB in adipocytes, suggesting that C/EBP is also involved in the repression 
      of NF-kappaB in adipocytes. These results suggested novel mechanisms by which 
      TNF-alpha selectively deletes adipocytes in the adipose tissue. The C/EBP- and 
      PPARgamma-mediated suppression of NF-kappaB may contribute to TNF-alpha-related 
      loss of adipose tissue mass under certain pathological situations, such as 
      cachexia.
FAU - Tamai, Minori
AU  - Tamai M
AD  - Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine 
      and Engineering, University of Yamanashi, Chuo, Yamanashi, Japan.
FAU - Shimada, Tsuyoshi
AU  - Shimada T
FAU - Hiramatsu, Nobuhiko
AU  - Hiramatsu N
FAU - Hayakawa, Kunihiro
AU  - Hayakawa K
FAU - Okamura, Maro
AU  - Okamura M
FAU - Tagawa, Yasuhiro
AU  - Tagawa Y
FAU - Takahashi, Shuhei
AU  - Takahashi S
FAU - Nakajima, Shotaro
AU  - Nakajima S
FAU - Yao, Jian
AU  - Yao J
FAU - Kitamura, Masanori
AU  - Kitamura M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100621
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR gamma)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
EIN - Lab Invest. 2017 Feb;97(2):228. PMID: 28133363
MH  - 3T3-L1 Cells
MH  - *Adipocytes/cytology/drug effects/metabolism
MH  - Animals
MH  - CCAAT-Enhancer-Binding Proteins/*genetics/metabolism/pharmacology
MH  - Cell Differentiation/drug effects/genetics/physiology
MH  - Cell Nucleus/genetics/metabolism
MH  - Mice
MH  - NF-kappa B/genetics/*metabolism/pharmacology
MH  - PPAR gamma/genetics/*metabolism/pharmacology
MH  - Sequence Deletion/drug effects
MH  - Tumor Necrosis Factor-alpha/genetics/metabolism/*pharmacology
MH  - Up-Regulation/drug effects
EDAT- 2010/06/23 06:00
MHDA- 2010/09/30 06:00
CRDT- 2010/06/23 06:00
PHST- 2010/06/23 06:00 [entrez]
PHST- 2010/06/23 06:00 [pubmed]
PHST- 2010/09/30 06:00 [medline]
AID - S0023-6837(22)02873-2 [pii]
AID - 10.1038/labinvest.2010.118 [doi]
PST - ppublish
SO  - Lab Invest. 2010 Sep;90(9):1385-95. doi: 10.1038/labinvest.2010.118. Epub 2010 
      Jun 21.