Targets for TNF-α-induced lipolysis in human adipocytes
M Rydén, E Arvidsson, L Blomqvist, L Perbeck… - Biochemical and …, 2004 - Elsevier
M Rydén, E Arvidsson, L Blomqvist, L Perbeck, A Dicker, P Arner
Biochemical and biophysical research communications, 2004•ElsevierBackground. Tumor necrosis factor-α (TNF-α)-induced lipolysis may be important for insulin
resistance in both obesity and cachexia. In rodent cells TNF-α enhances lipolysis through
down-regulation of the expression of the membrane proteins Gαi and the lipid droplet-
associated protein perilipin (PLIN). In human (but not murine) adipocytes TNF-α 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 Gαi. Methods. Gαi and PLIN as down …
resistance in both obesity and cachexia. In rodent cells TNF-α enhances lipolysis through
down-regulation of the expression of the membrane proteins Gαi and the lipid droplet-
associated protein perilipin (PLIN). In human (but not murine) adipocytes TNF-α 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 Gαi. Methods. Gαi and PLIN as down …
Background
Tumor necrosis factor-α (TNF-α)-induced lipolysis may be important for insulin resistance in both obesity and cachexia. In rodent cells TNF-α enhances lipolysis through down-regulation of the expression of the membrane proteins Gαi and the lipid droplet-associated protein perilipin (PLIN). In human (but not murine) adipocytes TNF-α 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 Gαi.
Methods
Gαi and PLIN as down-stream effectors of MAPKs were assessed in human adipocytes stimulated with TNF-α in the absence or presence of specific MAPK inhibitors.
Results
A 48-h incubation with TNF-α 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-α did not affect Gαi mRNA or protein expression. Furthermore, experiments with pertussis toxin demonstrated that inhibition of Gαi signaling did not affect TNF-α-mediated lipolysis.
Conclusions
Our results suggest that TNF-α-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, Gαi does not appear to be essential for TNF-α-induced lipolysis in human adipocytes.
Elsevier