PMID- 17272828
OWN - NLM
STAT- MEDLINE
DCOM- 20070622
LR  - 20210217
IS  - 0022-2275 (Print)
IS  - 0022-2275 (Linking)
VI  - 48
IP  - 5
DP  - 2007 May
TI  - NF-kappaB is important for TNF-alpha-induced lipolysis in human adipocytes.
PG  - 1069-77
AB  - Tumor necrosis factor-alpha (TNF-alpha) promotes lipolysis in mammal adipocytes 
      via the mitogen-activated protein kinase (MAPK) family, resulting in reduced 
      expression/function of perilipin (PLIN). The role of another pivotal 
      intracellular messenger activated by TNF-alpha, nuclear factor-kappaB 
      (NF-kappaB), has not been recognized. We explored the role of NF-kappaB in 
      TNF-alpha-induced lipolysis of human fat cells. Primary cultures of human 
      adipocytes were incubated in the presence of a cell-permeable peptide that 
      inhibits NF-kappaB signaling (WP). Incubation with WP, but not with a 
      biologically inactive peptide (MP), abolished the nuclear translocation of 
      NF-kappaB and effectively abrogated TNF-alpha-induced lipolysis in a 
      concentration-dependent manner. Western blot analysis demonstrated that although 
      TNF-alpha per se reduced mainly PLIN protein expression, TNF-alpha in the 
      presence of WP resulted in a pronounced combined reduction of both 
      hormone-sensitive lipase (HSL) and PLIN protein. The expression of a set of other 
      lipolytic or adipocyte-specific proteins was not affected. The regulation was 
      presumably at the transcriptional level, because mRNA expression for HSL and PLIN 
      was markedly reduced with TNF-alpha in the presence of NF-kappaB inhibition. This 
      was confirmed in gene reporter assays using human PLIN and HSL promoter 
      constructs. We conclude that in the presence of NF-kappaB inhibition, 
      TNF-alpha-mediated lipolysis is reduced, which suggests that NF-kappaB is 
      essential for retained human fat cell lipolysis.
FAU - Laurencikiene, Jurga
AU  - Laurencikiene J
AD  - Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 
      Huddinge, 141 86 Stockholm, Sweden.
FAU - van Harmelen, Vanessa
AU  - van Harmelen V
FAU - Arvidsson Nordstrom, Elisabet
AU  - Arvidsson Nordstrom E
FAU - Dicker, Andrea
AU  - Dicker A
FAU - Blomqvist, Lennart
AU  - Blomqvist L
FAU - Naslund, Erik
AU  - Naslund E
FAU - Langin, Dominique
AU  - Langin D
FAU - Arner, Peter
AU  - Arner P
FAU - Ryden, Mikael
AU  - Ryden M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070201
PL  - United States
TA  - J Lipid Res
JT  - Journal of lipid research
JID - 0376606
RN  - 0 (Carrier Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Peptides)
RN  - 0 (Perilipin-1)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Adipocytes/*drug effects/*metabolism
MH  - Carrier Proteins
MH  - Cell Membrane Permeability/drug effects
MH  - Cells, Cultured
MH  - Down-Regulation
MH  - Humans
MH  - Lipolysis/*drug effects
MH  - NF-kappa B/*metabolism
MH  - Peptides/pharmacology
MH  - Perilipin-1
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - RNA, Messenger/genetics
MH  - Signal Transduction
MH  - Transcription, Genetic/genetics
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2007/02/03 09:00
MHDA- 2007/06/23 09:00
CRDT- 2007/02/03 09:00
PHST- 2007/02/03 09:00 [pubmed]
PHST- 2007/06/23 09:00 [medline]
PHST- 2007/02/03 09:00 [entrez]
AID - S0022-2275(20)43553-9 [pii]
AID - 10.1194/jlr.M600471-JLR200 [doi]
PST - ppublish
SO  - J Lipid Res. 2007 May;48(5):1069-77. doi: 10.1194/jlr.M600471-JLR200. Epub 2007 
      Feb 1.