The involvement of NLRX1 and NLRP3 in the development of nonalcoholic steatohepatitis in mice.

ABSTRACT

BACKGROUND: Increasing evidence suggests that innate immunity is involved in the development of nonalcoholic fatty liver disease. Nod-like receptors (NLRs) have recently been identified as key mediators of inflammatory and immune responses. The aim of this article is to explore the correlation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR)X1 and NLRP3 with nonalcoholic steatohepatitis (NASH) in mice. METHODS: In our study, a high-fat diet, lipopolysaccharides (LPSs), and normal diet were given to C57BL mice to establish high fat (HF), HF + LPS, and control groups. Thereafter, serum alanine and aspartate aminotransferase (ALT and AST) levels were measured, and NASH severity was histologically examined. We measured tumor necrosis factor (TNF)-α levels by enzyme-linked immunosorbent assay, protein expression by Western blotting, and mRNA expression by real-time fluorescent quantitative reverse transcription-polymerase chain reaction. RESULTS: Levels of ALT and AST were higher in HF + LPS mice than in HF mice (p < 0.05). NLRX1 mRNA and protein expression was lower in HF and HF + LPS mice than in control mice (p < 0.05). NLRP3 mRNA expression was higher in HF and HF + LPS mice than in control mice (p < 0.05). The mRNA and protein expression of TNF receptor-associated factor (TRAF)6, interleukin-1ß, caspase-1, and apoptosis-associated speck-like protein were significantly higher in HF + LPS mice than in control and HF mice; furthermore, mRNA expression was higher in HF mice than in control mice (p < 0.05), but protein expression was similar. CONCLUSION: NLRX1 and NLRP3 inflammasomes may be important in NASH development.