PMID- 11694522
OWN - NLM
STAT- MEDLINE
DCOM- 20020207
LR  - 20220310
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 2
DP  - 2002 Jan 11
TI  - Mapping of early signaling events in tumor necrosis factor-alpha -mediated 
      lipolysis in human fat cells.
PG  - 1085-91
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine with a proposed 
      role in obesity-related insulin resistance. This could be mediated by increased 
      lipolysis in adipose tissue resulting in elevated free fatty acid levels. The 
      early intracellular signals entailed in TNF-alpha-mediated lipolysis are unknown 
      but may involve members of the mitogen-activated protein kinase (MAPK) family. We 
      investigated the possible contribution of MAPK in TNF-alpha-induced lipolysis in 
      human preadipocytes. TNF-alpha activated the three mammalian MAPK, p44/42, JNK, 
      and p38, in a distinct time- and concentration-dependent manner. TNF-alpha also 
      induced a concentration-dependent stimulation of lipolysis with a more than 
      3-fold increase at the maximal dose. Lipolysis was completely inhibited by 
      blockers specific for p44/42 (PD98059) and JNK (dimetylaminopurine) but was not 
      affected by the p38 blocker SB203580. Use of receptor-specific TNF-alpha mutants 
      showed that activation of MAPK is entirely mediated by the TNFR1 receptor. The 
      results in human preadipocytes differed from those obtained in murine 3T3-L1 
      adipocytes in which all three MAPK were constitutively active. Thus, studies of 
      intracellular signaling pathways obtained in different cellular contexts should 
      be interpreted with caution. In conclusion, although TNF-alpha activates all 
      three known MAPK in human preadipocytes, only p44/42 and JNK appear to be 
      involved in the regulation of lipolysis.
FAU - Ryden, Mikael
AU  - Ryden M
AD  - Lipid laboratory, Department of Medicine and Surgery, Karolinska Institute, 
      Huddinge University Hospital, S-141 86 Huddinge, Stockholm, Sweden.
FAU - Dicker, Andrea
AU  - Dicker A
FAU - van Harmelen, Vanessa
AU  - van Harmelen V
FAU - Hauner, Hans
AU  - Hauner H
FAU - Brunnberg, Martin
AU  - Brunnberg M
FAU - Perbeck, Leif
AU  - Perbeck L
FAU - Lonnqvist, Fredrik
AU  - Lonnqvist F
FAU - Arner, Peter
AU  - Arner P
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20011101
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Antigens, CD)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 649SA4S2CV (N(6),N(6)-dimethyladenine)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - JAC85A2161 (Adenine)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Adenine/*analogs & derivatives/pharmacology
MH  - Adipocytes/drug effects/*metabolism
MH  - Adult
MH  - Animals
MH  - Antigens, CD/metabolism
MH  - Cell Survival
MH  - Cells, Cultured
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Humans
MH  - Lipolysis/drug effects/*physiology
MH  - Mice
MH  - Middle Aged
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Phosphorylation
MH  - Receptors, Tumor Necrosis Factor/agonists/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Signal Transduction/*physiology
MH  - Tumor Necrosis Factor-alpha/genetics/*pharmacology
EDAT- 2001/11/06 10:00
MHDA- 2002/02/08 10:01
CRDT- 2001/11/06 10:00
PHST- 2001/11/06 10:00 [pubmed]
PHST- 2002/02/08 10:01 [medline]
PHST- 2001/11/06 10:00 [entrez]
AID - S0021-9258(20)87898-3 [pii]
AID - 10.1074/jbc.M109498200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Jan 11;277(2):1085-91. doi: 10.1074/jbc.M109498200. Epub 2001 
      Nov 1.