Different n-6/n-3 PUFA diets with fish oil attenuated osteoarthritis in ovariectomized mice via targeting the NLRP3 inflammasome. (February 2022)

• Record Type: Journal Article
• Authors: Zhang, Tianqi; Bai, Xiaolin; Dai, Yufeng; Dong, Ping; Wang, Jingfeng
• Is Part Of: Food bioscience. Volume 45(2022)
• Publication Date: 2022-02
• Subjects: n-3 PUFAs -- n-6 PUFAs -- Osteoarthritis -- Osteoporosis -- Fish oil -- NLRP3; Food -- Biotechnology -- Periodicals; Food -- Research -- Periodicals; Aliments -- Biotecnologia -- Revistes; Aliments -- Investigació -- Revistes; Food -- Biotechnology; Food -- Research; Revistes electròniques; Periodicals; 664.005
• DOI: 10.1016/j.fbio.2021.101220
• Languages: English
• ISSNs: 2212-4292

Abstract

Abstract: Osteoporosis(OP) and osteoarthritis(OA) co-exist with increased inflammatory cytokines as a common feature. Modern diet containing high n-6/n-3 PUFA was suggested contributing to these chronic inflammatory diseases. Although fish oil (FO) rich in n-3 PUFAs has been confirmed beneficial for OA and bone loss in previous studies, whether small amounts of FO could alleviate osteoporotic OA under a high n-6/n-3 PUFA condition has not been reported. In this study, the osteoporotic OA mice were fed with 20:1 or 6:1 n-6/n-3 PUFA diets with or without FO for 12 weeks. The results showed that 20:1 diet with FO ameliorated systemic inflammation and cartilage degradation in model mice, compared to the non-FO 20:1 diet. Specifically, diets with FO altered the fatty acids composition with elevating n-3/n-6 PUFA in articular cartilage, thus restoring the cartilage homeostasis by inhibiting the catabolic process. Mechanistically, 20:1 non-FO diet promoted the expression of NLRP3 via PGE2/EP4/NFκB. However, 20:1 FO-H diet significantly inhibited the expression of NLRP3 and further exhibited a greater affinity for GPR120 than 20:1 non-FO diet to inactivate caspase-1-dependent NLRP3 inflammasome. As a consequence, 20:1 FO-H diet inhibited chondrocyte pyroptosis and followed by the reduction of the two catabolic cytokines: IL-1β and IL-18. Notably, the 20:1 FO-H diet performed as well as the 6:1 non-FO diet, and 6:1 diet with FO could further improve osteoporotic OA in a dose-dependent manner. This study demonstrated that FO could attenuate the adverse effect of 20:1 n-6/n-3 PUFA diet on osteoporotic OA, providing skeletal evidence for healthy diet. Graphical abstract: Non-FO 20:1 n-6/n-3 PUFA diet increased the content of PGE2 in synovial fluid and the expression of its receptor EP4, which activated the inflammasome executive protein caspase-1 through the EP4/NFkB/NLRP3 pathway, causing the chondrocytes pyroptosis accompanied by a large release of inflammatory factors IL-18 and IL-1β, and finally leading to cartilage degeneration.20:1 n-6/n-3 PUFA diet with FO could increase the expression of β-arrestin through GPR120 and directly inhibit the self-assembly of NLRP3 inflammasomes, thereby attenuating osteoarthritis. Image 1