Tumor necrosis factor α stimulates lipolysis in adipocytes by decreasing G(i) protein concentrations

Slavisa Gasic, Bing Tian, Allan Green

Research output: Contribution to journalArticle

113 Scopus citations

Abstract

Prolonged treatment (12-24 h) of adipocytes with tumor necrosis factor α (TNFα) stimulates lipolysis. We have investigated the hypothesis that TNFα stimulates lipolysis by blocking the action of endogenous adenosine. Adipocytes were incubated for 48 h with TNFα, and lipolysis was measured in the absence or presence of adenosine deaminase. Without adenosine deaminase, the rate of glycerol release was 2-3-fold higher in the TNFα-treated cells, but with adenosine deaminase lipolysis increased in the controls to approximately that in the TNFα-treated cells. This suggests that TNFα blocks adenosine release or prevents its antilipolytic effect. Both N(G)- phenylisopropyl adenosine and nicotinic acid were less potent and efficacious inhibitors of lipolysis in treated cells. A decrease in the concentration of α-subunits of all three G(i) subtypes was detected by Western blotting without a change in G(s) proteins or β-subunits. G(i2)α was about 50% of control, whereas G(i1)α and G(i3)α were about 20 and 40% of control values, respectively. The time course of G(i) down-regulation correlated with the stimulation of lipolysis. Furthermore, down-regulation of G(i) by an alternative approach (prolonged incubation with N(G)-phenylisopropyl adenosine) stimulated lipolysis. These findings indicate that TNFα stimulates lipolysis by blunting endogenous inhibition of lipolysis. The mechanism appears to be a G(i) protein down-regulation.

Original languageEnglish (US)
Pages (from-to)6770-6775
Number of pages6
JournalJournal of Biological Chemistry
Volume274
Issue number10
DOIs
StatePublished - Mar 5 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Tumor necrosis factor α stimulates lipolysis in adipocytes by decreasing G(i) protein concentrations'. Together they form a unique fingerprint.

  • Cite this