Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 425217
Title The Inflammasome and Caspase-1 Activation: A New Mechanism Underlying Increased Inflammatory Activity in Human Visceral Adipose Tissue
Author(s) Koenen, T.B.; Stienstra, R.; Tits, L.J. van; Joosten, L.A.B.; Velzen, J.F.; Hijmans, A.; Pol, J.A.; Vliet, J.A. van der; Netea, M.G.; Tack, C.J.; Stalenhoef, A.F.H.; Graaf, J. de
Source Endocrinology 152 (2011)10. - ISSN 0013-7227 - p. 3769 - 3778.
DOI http://dx.doi.org/10.1210/en.2010-1480
Department(s) Chair Nutrition Metabolism and Genomics
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2011
Keyword(s) necrosis-factor-alpha - insulin-resistance - nalp3 inflammasome - metabolic syndrome - abdominal obesity - human adipocytes - crucial role - interleukin-1-beta - plasma - macrophages
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)
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