Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation
Dietary saturated fatty acid and polyunsaturated fatty acid oppositely affect hepatic NOD-like receptor protein 3 inflammasome through regulating nuclear factor-kappa B activation
复制标题
膳食饱和脂肪酸和多不饱和脂肪酸通过调节核因子-κ B活化对肝脏NOD样受体蛋白3炎性小体的影响
DOI：
10.3748/wjg.v22.i8.2533
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发表时间：
2016-02-28
影响因子：
4.3
通讯作者：
Hua, Jing
中科院分区：
文献类型：
--
作者：
Sui, Yong-Heng;Luo, Wen-Jing;Hua, Jing
目的：方法：采用高脂饲料和富含多不饱和脂肪酸（PUFA）饲料喂养野生型C57 BL/ 6小鼠，观察不同膳食脂肪酸对肝脏炎性小体激活的影响。用饱和脂肪酸（SFA）或PUFA以及与脂多糖（LPS）组合处理原代肝细胞。实时定量PCR和Western blot检测NOD样受体蛋白3（NLRP 3）、炎性小体、过氧化物酶体增殖物激活受体γ（Peroxisome Proliferator-Activated Receptor-γ）和核因子κ B（NF-κ B）的表达。结果：高脂饮食诱导的肝脂肪变性足以诱导和激活肝脏NLRP 3炎性小体。SFA棕榈酸（PA）直接激活NLRP 3炎性小体，并增加对肝细胞中LPS诱导的炎性小体激活的敏感性。相反，PUFA二十二碳六烯酸（DHA）有可能抑制肝细胞中NLRP 3炎性小体的表达，并部分消除LPS诱导的NLRP 3炎性小体激活。此外，高脂饮食增加，但富含PUFA的饮食降低了体内对LPS诱导的肝脏NLRP 3炎性小体激活的敏感性。结论：肝脏NLRP 3炎性小体激活在非酒精性脂肪肝的发生发展中起重要作用。日粮中的SFAs和PUFAs通过直接激活或抑制NF-κ B而反向调节NLRP 3炎性体的活性。
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-gamma and nuclear factor-kappa B (NF-kappa B) was determined by real-time PCR and Western blot. The activity of Caspase-1 and interleukine-1 beta 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-kappa B 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-kappa B.