Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2533
Peer-review started: July 1, 2015
First decision: September 29, 2015
Revised: October 17, 2015
Accepted: December 30, 2015
Article in press: December 30, 2015
Published online: February 28, 2016
Processing time: 242 Days and 3.1 Hours
AIM: To investigate the effect of different dietary fatty acids on hepatic inflammasome activation.
METHODS: Wild-type C57BL/6 mice were fed either a high-fat diet or polyunsaturated fatty acid (PUFA)-enriched diet. Primary hepatocytes were treated with either saturated fatty acids (SFAs) or PUFAs as well as combined with lipopolysaccharide (LPS). The expression of NOD-like receptor protein 3 (NLRP3) inflammasome, peroxisome proliferator-activated receptor-γ and nuclear factor-kappa B (NF-κB) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1β production were measured.
RESULTS: High-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NLRP3 inflammasome. SFA palmitic acid (PA) directly activated NLRP3 inflammasome and increased sensitization to LPS-induced inflammasome activation in hepatocytes. In contrast, PUFA docosahexaenoic acid (DHA) had the potential to inhibit NLRP3 inflammasome expression in hepatocytes and partly abolished LPS-induced NLRP3 inflammasome activation. Furthermore, a high-fat diet increased but PUFA-enriched diet decreased sensitization to LPS-induced hepatic NLRP3 inflammasome activation in vivo. Moreover, PA increased but DHA decreased phosphorylated NF-κB p65 protein expression in hepatocytes.
CONCLUSION: Hepatic NLRP3 inflammasome activation played an important role in the development of non-alcoholic fatty liver disease. Dietary SFAs and PUFAs oppositely regulated the activity of NLRP3 inflammasome through direct activation or inhibition of NF-κB.
Core tip: Our research inventively elucidated that high-fat diet-induced hepatic steatosis was sufficient to induce and activate hepatic NOD-like receptor protein 3 (NLRP3) inflammasome, playing an important role in the development of non-alcoholic fatty liver disease. Furthermore, dietary saturated fatty acids and polyunsaturated fatty acids oppositely regulated the activity of NLRP3 inflammasome in hepatocytes and transmitted different sensitization to lipopolysaccharide-induced activation of NLRP3 inflammasome in vitro and in vivo, partly through direct activation or inhibition of nuclear factor-kappa B.