Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Internal Postal Code 463, Geert Grooteplein 8, 6500 HB Nijmegen, The Netherlands.
Endocrinology. 2011 Oct;152(10):3769-78. doi: 10.1210/en.2010-1480. Epub 2011 Aug 23.
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-1β 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-1β (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.
具有免疫能力的腹部脂肪组织，无论是储存于内脏（内脏脂肪组织[VAT]）还是皮下（皮下脂肪组织[SAT]），都已被确定为白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的来源。为了变得活跃，这些细胞因子的前体需要半胱天冬酶-1（caspase-1）的加工，而半胱天冬酶-1本身又受到炎性小体的介导。在这项描述性研究中，我们调查了人脂肪中炎性小体成分和半胱天冬酶-1 的表达，并确定半胱天冬酶-1 活性是否有助于 VAT 增强的炎症状态。从 10 名超重受试者（体重指数为 25-28 kg/m2）中取出配对的 SAT 和 VAT 活检，以研究两个脂肪组织库的细胞组成和内在炎症能力。与 SAT 相比，VAT 中淋巴细胞部分的 CD8+T 细胞百分比明显更高（41.6%比 30.4%；P<0.05）。与 SAT 相比，VAT 释放的白细胞介素-1β（10 倍；P<0.05）、白细胞介素-18（3 倍；P<0.05）、白细胞介素-6 和白细胞介素-8（3 倍，P<0.05；4 倍，P<0.05）均显著减少。抑制半胱天冬酶-1 活性后，VAT 中 caspase-1 的活性也增加了 3 倍（P<0.05），炎性小体成员凋亡相关斑点样蛋白含有 C 端半胱氨酸募集结构域（2 倍；P<0.05）和核苷酸结合寡聚化结构域样受体包含 pyrin 结构域 3（2 倍；无显著意义）的蛋白水平也增加。最后，半胱天冬酶-1 活性水平与脂肪组织中存在的 CD8+T 细胞百分比呈正相关。我们的结果表明，半胱天冬酶-1 和核苷酸结合寡聚化结构域样受体包含 pyrin 结构域 3 的炎性小体成员在人 VAT 中大量存在。VAT 中固有半胱天冬酶-1 活性的增加代表了一种新的、特定的炎症途径，可能决定了这一特定脂肪库的促炎特性。
