Docosahexaenoic acid ameliorates palmitate-induced lipid accumulation and inflammation through repressing NLRC4 inflammasome activation in HepG2 cells.

ABSTRACT: BACKGROUND: N-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA; 22:6n-3), has clinical significance in the prevention and reversal of nonalcoholic steatohepatitis (NASH). However, the precious mechanism underlying remains unclear. The inflammasome, a multiprotein complex formed by NOD-like receptor (NLR) family members, has been recently shown to be activated in NASH and promote the cleavage of the pro-inflammatory cytokines to their maturation forms. METHODS: HepG2 cells were exposed to different dose of PA for 24?h with or without the preincubation of 50??M DHA for another 24?h and then lipid deposition was assessed with Oil red O staining and intracellular triglyceride (TG) determination. Secretory levels of inflammatory cytokines and Caspase-1 activity were determined by ELISA assays. Gene expression and protein levels were determined by quantitative RCR and western blotting, respectively. RESULTS: Palmitate (PA) dose-dependently increased lipid accumulation, TG content and induced the secretion of interleukin-1? (IL-1?), IL-18, TNF-? and MCP-1 from HepG2 cells. Preincubation with DHA significantly alleviated PA-induced lipid accumulation and inflammatory agents. DHA was also found to attenuate PA-induced NOD-like receptor protein 4 (NLRC4) mRNA expression. Furthermore, PA induced caspase-1 activation in a dose-dependent manner, resulting in exacerbating of procaspase-1 and pro-IL-1? processing. Knockdown of NLRC4 partially abrogated PA-induced caspase-1 activation and IL-1? maturation and completely abolished these events in the presence of DHA. CONCLUSIONS: Our findings indicate DHA attenuates PA-induced lipid accumulation and inflammation through suppressing NLRC4 inflammasome activation, caspase-1 activation and IL-1? cleavage.

SUBMITTER: Luo X 

PROVIDER: S-EPMC3428681 | biostudies-other | 2012

REPOSITORIES: biostudies-other