n-3多不饱和脂肪酸加重FFAR4基因缺失小鼠结肠炎进程

n-3 Polyunsaturated Fatty Acids Exacerbate Colitis Progress in FFAR4 Knockout Mice

摘要:

炎症性肠病（inflammatory bowel disease, IBD）是一种慢性肠道疾病，额外营养支持有助于缓解IBD患者病情。研究表明膳食中n-3多不饱和脂肪酸具有良好的抗炎作用，而人群研究表明部分IBD患者额外补充n-3多不饱和脂肪酸无益于其疾病缓解。大规模测序发现n-3多不饱和脂肪酸受体基因FFAR4存在突变，n-3多不饱和脂肪酸在IBD治疗中的不确定结果是否与FFAR4基因的缺失有关，目前尚不清晰。通过对野生型（WT）小鼠和FFAR4基因缺失（FFAR4KO）小鼠进行结肠炎造模，并同时对两组小鼠额外补充n-3多不饱和脂肪酸，实验结果表明，在同时补充n-3多不饱和脂肪酸的情况下，相较于WT小鼠，FFAR4KO小鼠的结肠炎更加严重，表现为更多的体质量丢失、更高的疾病活动指数（disease activity index，DAI）、更高的结肠髓过氧化物酶（MPO）活性以及更高的结肠炎症因子转录水平。该研究为IBD患者得到精确营养干预提供了理论依据。

Abstract:

Inflammatory bowel disease(IBD) is a chronic intestinal inflammatory disease, and additional nutritional support contributes to alleviate IBD symptoms. Studies have shown that dietary n-3 polyunsaturated fatty acids possess anti-inflammatory activity, while clinical trials have reported that additional supplementation with n-3 polyunsaturated fatty acids does not alleviate the disease symptoms in some IBD patients. Large-scale sequencing has revealed mutations in the n-3 polyunsaturated fatty acids receptor gene free fatty acid receptor 4(FFAR4). It remains unclear whether the variable effects of n-3 polyunsaturated fatty acids in IBD treatment are associated with the absence of the FFAR4 gene. In this study, the wild type(WT) and FFAR4 knockout (FFAR4KO) mice were used to establish the colitis models, concurrently supplemented with n-3 polyunsaturated fatty acids. The results showed that compared to those WT mice, the FFAR4KO mice exhibited more severer colitis under simultaneous n-3 polyunsaturated fatty acids supplementation, characterized by greater weight loss, higher disease activity index(DAI), increased colonic myeloperoxidase (MPO) activity, and higher mRNA levels of colonic inflammatory factors. This study provides a theoretical basis for precise nutritional intervention in IBD patients.