The ATP-P2X7 signalling axis is dispensable for obesity-associated inflammasome activation in adipose tissue

S. Sun, S. Xia, Y. Ji, A.H. Kersten, L. Qi

Research output: Contribution to journalArticleAcademicpeer-review

56 Citations (Scopus)

Abstract

Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% high-fat diet (HFD), coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X7 in adipose tissue. Unexpectedly, P2X7-deficient animals on HFD exhibit no changes in metabolic phenotypes, inflammatory responses, or inflammasome activation when compared with the wild-type controls. Similar observations have been obtained in hematopoietic cell–specific P2X7-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia but, unexpectedly, is not mediated by the ATP-P2X7 signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized.
Original languageEnglish
Pages (from-to)1471-1478
JournalDiabetes
Volume61
Issue number6
DOIs
Publication statusPublished - 2012

Keywords

  • p2 purinergic receptors
  • necrosis-factor-alpha
  • insulin-resistance
  • extracellular atp
  • adipocyte death
  • rat adipocytes
  • expression
  • p2x(7)
  • macrophages
  • mice

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