PMID- 15110769
OWN - NLM
STAT- MEDLINE
DCOM- 20040608
LR  - 20161124
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 318
IP  - 1
DP  - 2004 May 21
TI  - Targets for TNF-alpha-induced lipolysis in human adipocytes.
PG  - 168-75
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha)-induced lipolysis may be 
      important for insulin resistance in both obesity and cachexia. In rodent cells 
      TNF-alpha enhances lipolysis through down-regulation of the expression of the 
      membrane proteins Galpha(i) and the lipid droplet-associated protein perilipin 
      (PLIN). In human (but not murine) adipocytes TNF-alpha stimulates lipolysis 
      through the mitogen activated protein kinases (MAPKs) p44/42 and JNK although it 
      is unclear whether this is mediated via PLIN and/or Galpha(i). METHODS: Galpha(i) 
      and PLIN as down-stream effectors of MAPKs were assessed in human adipocytes 
      stimulated with TNF-alpha in the absence or presence of specific MAPK inhibitors. 
      RESULTS: A 48-h incubation with TNF-alpha resulted in a pronounced increase in 
      lipolysis, which was paralleled by a decrease in the mRNA and protein expression 
      of PLIN. Both these effects were inhibited in a concentration-dependent manner in 
      the presence of MAPK inhibitors specific for p44/42 (PD98059) and JNK (SP600125). 
      However, TNF-alpha did not affect Galpha(i) mRNA or protein expression. 
      Furthermore, experiments with pertussis toxin demonstrated that inhibition of 
      Galpha(i) signaling did not affect TNF-alpha-mediated lipolysis. CONCLUSIONS: Our 
      results suggest that TNF-alpha-mediated lipolysis is dependent on down-regulation 
      of PLIN expression via p44/42 and JNK. This could be an important mechanism for 
      the development of insulin resistance in both obesity and cachexia. However, in 
      contrast to findings in rodent cells, Galpha(i) does not appear to be essential 
      for TNF-alpha-induced lipolysis in human adipocytes.
FAU - Ryden, Mikael
AU  - Ryden M
AD  - Department of Medicine M63, Karolinska Institutet, Karolinska University Hospital 
      at Huddinge, 141 86 Stockholm, Sweden. mikael.ryden@medhs.ki.se
FAU - Arvidsson, Elisabet
AU  - Arvidsson E
FAU - Blomqvist, Lennart
AU  - Blomqvist L
FAU - Perbeck, Leif
AU  - Perbeck L
FAU - Dicker, Andrea
AU  - Dicker A
FAU - Arner, Peter
AU  - Arner P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Perilipin-1)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.4.2.31 (Pertussis Toxin)
SB  - IM
MH  - Adipocytes/cytology/*drug effects/*metabolism
MH  - Adolescent
MH  - Adult
MH  - Carrier Proteins
MH  - Cell Differentiation
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Lipolysis/drug effects/*physiology
MH  - Male
MH  - Membrane Proteins/antagonists & inhibitors/biosynthesis
MH  - Middle Aged
MH  - Perilipin-1
MH  - Pertussis Toxin/pharmacology
MH  - Phosphoproteins/biosynthesis
MH  - RNA, Messenger/biosynthesis
MH  - Tumor Necrosis Factor-alpha/*pharmacology
EDAT- 2004/04/28 05:00
MHDA- 2004/06/21 10:00
CRDT- 2004/04/28 05:00
PHST- 2004/03/17 00:00 [received]
PHST- 2004/04/28 05:00 [pubmed]
PHST- 2004/06/21 10:00 [medline]
PHST- 2004/04/28 05:00 [entrez]
AID - S0006291X0400717X [pii]
AID - 10.1016/j.bbrc.2004.04.010 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2004 May 21;318(1):168-75. doi: 
      10.1016/j.bbrc.2004.04.010.