The Inflammasome and Caspase-1 Activation: A New Mechanism Underlying Increased Inflammatory Activity in Human Visceral Adipose Tissue

T.B. Koenen, R. Stienstra, L.J. van Tits, L.A.B. Joosten, J.F. Velzen, A. Hijmans, J.A. Pol, J.A. van der Vliet, M.G. Netea, C.J. Tack, A.F.H. Stalenhoef, J. de Graaf

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70 Citations (Scopus)

Abstract

The immune competent abdominal adipose tissue, either stored viscerally [visceral adipose tissue (VAT)] or sc [sc adipose tissue (SAT)], has been identified as a source of IL-1 beta and IL-18. To become active, the proforms of these cytokines require processing by caspase-1, which itself is mediated by the inflammasome. In this descriptive study, we investigate the expression of inflammasome components and caspase-1 in human fat and determine whether caspase-1 activity contributes to the enhanced inflammatory status of VAT. Paired SAT and VAT biopsies from 10 overweight subjects (body mass index, 25-28 kg/m(2)) were used to study the cellular composition and the intrinsic inflammatory capacity of both adipose tissue depots. The percentage of CD8(+) T cells within the lymphocyte fraction was significantly higher in VAT compared with SAT (41.6 vs. 30.4%; P <0.05). Adipose tissue cultures showed a higher release of IL-1 beta (10-fold; P <0.05), IL-18 (3-fold; P <0.05), and IL-6 and IL-8 (3-fold, P <0.05; and 4-fold, P <0.05, respectively) from VAT compared with SAT that was significantly reduced by inhibiting caspase-1 activity. In addition, caspase-1 activity was 3-fold (P <0.05) higher in VAT compared with SAT, together with an increase in the protein levels of the inflammasome members apoptosis-associated speck-like protein containing a C-terminal caspase-recruitment domain (2-fold; P <0.05) and nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (2-fold; nonsignificant). Finally, caspase-1 activity levels were positively correlated with the percentage of CD8(+) T cells present in adipose tissue. Our results show that caspase-1 and nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 inflammasome members are abundantly present in human VAT. The increased intrinsic caspase-1 activity in VAT represents a novel and specific inflammatory pathway that may determine the proinflammatory character of this specific depot. (Endocrinology 152: 3769-3778, 2011)
Original languageEnglish
Pages (from-to)3769-3778
JournalEndocrinology
Volume152
Issue number10
DOIs
Publication statusPublished - 2011

Keywords

  • necrosis-factor-alpha
  • insulin-resistance
  • nalp3 inflammasome
  • metabolic syndrome
  • abdominal obesity
  • human adipocytes
  • crucial role
  • interleukin-1-beta
  • plasma
  • macrophages

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