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

110 Citations (Scopus)

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

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Lipolysis
Adipocytes
Tumor Necrosis Factor-alpha
Adenosine
Proteins
Adenosine Deaminase
Down-Regulation
Cells
Niacin
Protein Subunits
Glycerol
Western Blotting

ASJC Scopus subject areas

  • Biochemistry

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Tumor necrosis factor α stimulates lipolysis in adipocytes by decreasing G(i) protein concentrations. / Gasic, Slavisa; Tian, Bing; Green, Allan.

In: Journal of Biological Chemistry, Vol. 274, No. 10, 05.03.1999, p. 6770-6775.

Research output: Contribution to journalArticle

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