Basic Study
Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Feb 28, 2016; 22(8): 2533-2544
Published online Feb 28, 2016. doi: 10.3748/wjg.v22.i8.2533
Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation
Yong-Heng Sui, Wen-Jing Luo, Qin-Yu Xu, Jing Hua
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
Author contributions: Sui YH and Luo WJ contributed equally to this work, performed the experiments and analyzed the data; Xu QY coordinated the research; Hua J designed the study; Sui YH, Luo WJ and Hua J wrote the paper.
Supported by The National Natural Science Foundation of China, NO. 81170374 and NO. 81470842 to Hua J.
Institutional review board statement: The study was reviewed and approved by Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Institutional Review Board.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University (IACUC protocol number: SYXK 2011-0121).
Conflict-of-interest statement: We declare that there is no conflict of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Jing Hua, MD, PhD, Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, No. 160 Pu Jian Road, Shanghai 200127, China. hua-jing88@hotmail.com
Telephone: +86-21-68383113 Fax: +86-21-63200874
Received: June 28, 2015
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
Abstract

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.

Keywords: Non-alcoholic fatty liver disease, NOD-like receptor protein 3 inflammasome, Saturated fatty acids, Polyunsaturated fatty acids, Nuclear factor-kappa B

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.