title: Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Yong-Heng Sui, Wen-Jing Luo, Qin-Yu Xu, Jing Hua, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200127, China.
authors.forename: Yong-Heng
authors.initials: YH
authors.lastname: Sui
authors.affiliation: Yong-Heng Sui, Wen-Jing Luo, Qin-Yu Xu, Jing Hua, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200127, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Luo
authors.affiliation: Yong-Heng Sui, Wen-Jing Luo, Qin-Yu Xu, Jing Hua, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200127, China.
authors.forename: Qin-Yu
authors.initials: QY
authors.lastname: Xu
authors.affiliation: Yong-Heng Sui, Wen-Jing Luo, Qin-Yu Xu, Jing Hua, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, Shanghai 200127, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hua
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D058847:Inflammasomes / Q000187:drug effects* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control; D047495:PPAR gamma / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology*; D010766:Phosphorylation; D061251:Primary Cell Culture; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*
chemical_list: C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D047495:PPAR gamma; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D004281:Docosahexaenoic Acids; D019308:Palmitic Acid; D020170:Caspase 1
keywords: NOD-like receptor protein 3 inflammasome; Non-alcoholic fatty liver disease; Nuclear factor-kappa B; Polyunsaturated fatty acids; Saturated fatty acids