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Lower NLRP3 inflammasome activity in NAG‐1 transgenic mice is linked to a resistance to obesity and increased insulin sensitivity
Author(s) -
Wang Xingya,
Chrysovergis Kali,
Kosak Justin,
Eling Thomas E.
Publication year - 2014
Publication title -
obesity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.438
H-Index - 199
eISSN - 1930-739X
pISSN - 1930-7381
DOI - 10.1002/oby.20638
Subject(s) - inflammasome , endocrinology , medicine , insulin resistance , leptin , adipose tissue , white adipose tissue , diet induced obese , obesity , insulin , caspase 1 , chemistry , biology , inflammation
Objective 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. Methods Key components of the NLRP3 inflammasome were examined in NAG‐1 Tg mice on both regular and high fat diet (HFD) conditions. Results 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. Conclusions 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.