Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences (NIEHS), 111. T.W. Alexander Dr, Research Triangle Park, North Carolina, USA.
Obesity (Silver Spring). 2014 May;22(5):1256-63. doi: 10.1002/oby.20638. Epub 2013 Dec 5.
The NLRP3 inflammasome plays an important regulatory role in obesity-induced insulin resistance. NSAID activated gene-1 (NAG-1) is a divergent member of the TGF-β superfamily. NAG-1 Tg mice are resistant to dietary- and genetic-induced obesity and have improved insulin sensitivity. The objective was to examine whether NLRP3 inflammasome activity is associated with this observed phenotype in NAG-1 Tg mice.
Key components of the NLRP3 inflammasome were examined in NAG-1 Tg mice on both regular and high fat diet (HFD) conditions.
The expression of caspase-1 and ASC, key components of the NLRP3 inflammasome, is significantly reduced at mRNA and protein levels in white adipose tissue (WAT) of NAG-1 Tg mice. HFD increases the expression of caspase-1 and ASC in WT mice, but their expression is reduced in NAG-1 Tg mice. Furthermore, there is reduced IL-18, IL-1β, and TNF-α expression in the WAT of NAG-1 Tg mice. NAG-1 Tg mice have significantly lower serum leptin and insulin levels and reduced expression of macrophage infiltration markers (F4/80, CD11b, and CD11c) in WAT.
The study suggests the lower NLRP3 inflammasome activity may play a role in the resistance of NAG-1 Tg mice to diet-induced obesity and improved insulin sensitivity.
NLRP3 炎性小体在肥胖诱导的胰岛素抵抗中起重要的调节作用。非甾体抗炎药激活基因-1（NAG-1）是 TGF-β 超家族的一个分支成员。NAG-1Tg 小鼠对饮食和遗传诱导的肥胖具有抗性，并改善了胰岛素敏感性。本研究旨在探讨 NLRP3 炎性小体的活性是否与 NAG-1Tg 小鼠的这种表型有关。
在正常饮食和高脂肪饮食（HFD）条件下，检测 NAG-1Tg 小鼠中 NLRP3 炎性小体的关键组成部分。
NAG-1Tg 小鼠白色脂肪组织（WAT）中 caspase-1 和 ASC 的表达，NLRP3 炎性小体的关键组成部分，在 mRNA 和蛋白水平上均显著降低。HFD 增加了 WT 小鼠中 caspase-1 和 ASC 的表达，但在 NAG-1Tg 小鼠中表达降低。此外，NAG-1Tg 小鼠的 WAT 中 IL-18、IL-1β 和 TNF-α 的表达减少。NAG-1Tg 小鼠的血清瘦素和胰岛素水平显著降低，WAT 中巨噬细胞浸润标志物（F4/80、CD11b 和 CD11c）的表达减少。
研究表明，NLRP3 炎性小体活性降低可能在 NAG-1Tg 小鼠对饮食诱导的肥胖和改善胰岛素敏感性的抵抗中起作用。
