Objective: To investigate the changes in gene expression related to intestinal fatty acid oxidation and carnitine metabolism in patients with ulcerative colitis (UC). Methods: A retrospective study was conducted involving patients with UC (UC group) and non-UC controls (control group) who underwent routine colonoscopy to exclude polyps at Peking Union Medical College Hospital between January 1, 2018, to December 31, 2023. Colon tissue samples were collected from both groups and RNA was extracted. Real-time fluorescence quantitative polymerase chain reaction technology was used to detect the mRNA expression levels of genes related to fatty acid oxidation and carnitine metabolism and to analyze their correlation with inflammatory gene expression. The expression of genes linked to fatty acid oxidation and carnitine metabolism was analyzed by analyzing the colonic mucosal transcriptome data of UC patients and controls in high-throughput gene expression database (GEO). Immunohistochemistry was used to examine the expression of the carnitine transporter SLC6A14 in the intestinal tissues of both groups at the protein level. Eight-week-old male C57BL/6 mice were selected and divided into a drinking water group (drinkind daily water) and a dextran sodium sulfate (DSS) group (drinking 2.5% DSS solution) with 4 mice in each group. DSS was used to induce an acute colitis model in mice and detect the difference in mRNA expression levels of SLC6A14 and interleukin-6 (IL-6) in the intestinal tissues of the both groups of mice. Results: A total of 22 patients were included in the UC group, with 12 males and 10 females, aged 16-64 (40±12) years. The control group consisted of 10 patients, with 3 males and 7 females, aged 43-72 (64±8) years. The UC group had lower mRNA expression levels of genes related to fatty acid oxidation and transport in the intestine compared to those in the control group, such as CD36 [0.40 (0.27, 0.55) vs 0.93 (0.39, 2.93)], CPT1A [0.39 (0.07, 0.54) vs 0.93 (0.41, 1.71)], CPT1B (0.37±0.36 vs 1.37±0.89), CPT2 [0.36 (0.30, 0.43) vs 1.14 (0.68, 1.34)], CRAT [0.31 (0.25, 0.41) vs 1.06 (0.64, 1.73)], CROT [0.14 (0.10, 0.21) vs 0.95 (0.77, 1.27)] (all P<0.05). The mRNA expression levels of genes related to carnitine transport in the UC group were lower than those in the control group, such as OCTN1 [0.18 (0.10, 0.41) vs 0.83 (0.41, 1.47)], OCTN2 [0.01 (0.00, 0.01) vs 0.47 (0.35, 2.15)] (both P<0.05). The mRNA expression levels of the carnitine transporter gene SLC6A14 in the intestine of UC patients was higher than that of the control group [11.31 (5.34, 23.50) vs 0.78 (0.07, 3.70), P<0.001], and showed a positive correlation with the inflammatory gene IL-6 (r=0.425, 95%CI: 0.076-0.681, P=0.019). Analysis of the GEO database revealed lower expression levels of CD36, CPT1A, CPT2, CRAT and CROT in UC group compared to controls (all P<0.05), while the expression levels of SLC6A14 were higher than those in control group (P<0.05). The protein expression level of SLC6A14 in colon tissue of UC group was higher than that of control group (0.45±0.07 vs 0.30±0.01, P=0.019). The mRNA expression of SLC6A14 in the intestine of DSS group was higher compared to that in the drinking water group (1.83±0.90 vs 0.60±0.10, P=0.035). Conclusion: The expression levels of genes associated with intestinal fatty acid oxidation and carnitine metabolism (CD36, CPT1A, CPT1B, CPT2, CRAT, CROT, OCTN1, and OCTN2) are decreased in UC patients, while the expression level of SLC6A14, a gene capable of transporting both amino acids and carnitine, is increased.
目的： 分析溃疡性结肠炎（UC）患者肠道脂肪酸氧化和肉碱代谢相关基因表达变化。 方法： 回顾性纳入2018年1月1日至2023年12月31日北京协和医院就诊的UC患者（UC组）和定期行结肠镜检查排除息肉的非UC对照者（对照组），收集2组结肠组织样本并提取RNA，采用实时荧光定量聚合酶链反应技术检测脂肪酸氧化和肉碱代谢相关基因的mRNA表达水平，并分析其与炎症基因表达的相关性。利用高通量基因表达数据库（GEO）中UC患者和对照者结肠黏膜转录组数据，分析脂肪酸氧化和肉碱代谢相关基因的表达情况。免疫组化检测2组肠道组织中肉碱转运蛋白SLC6A14的表达水平。选择8周龄雄性C57BL/6小鼠，分为饮水组（饮用日常水）及葡聚糖硫酸钠（DSS）组（饮用2.5% DSS溶液），每组各4只，利用DSS诱导小鼠急性结肠炎模型，检测2组小鼠肠道组织中的SLC6A14和白细胞介素-6（IL-6）的mRNA表达水平的差异。 结果： UC组共纳入22例患者，男12例，女10例，年龄16~64（40±12）岁；对照组10名，男3名，女7名，年龄43~72（64±8）岁。UC组肠道中与脂肪酸氧化及转运有关的基因mRNA表达水平低于对照组，如CD36［0.40（0.27，0.55）比0.93（0.39，2.93）］、CPT1A［0.39（0.07，0.54）比0.93（0.41，1.71）］、CPT1B（0.37±0.36比1.37±0.89）、CPT2［0.36（0.30，0.43）比1.14（0.68，1.34）］、CRAT［0.31（0.25，0.41）比1.06（0.64，1.73）］、CROT［0.14（0.10，0.21）比0.95（0.77，1.27）］（均P<0.05）；UC组肠道中与肉碱转运相关基因mRNA表达水平低于对照组，如OCTN1［0.18（0.10，0.41）比0.83（0.41，1.47）］、OCTN2［0.01（0.00，0.01）比0.47（0.35，2.15）］（均P<0.05）。UC患者肠道中肉碱转运蛋白编码基因SLC6A14的mRNA表达水平高于对照组［11.31（5.34，23.50）比0.78（0.07，3.70），P<0.001］，且与炎症基因IL-6表达呈正相关（r=0.425，95%CI：0.076～0.681，P=0.019）。GEO数据库分析发现，UC组与脂肪酸氧化、转运有关基因CD36、CPT1A、CPT2、CRAT、CROT的表达水平低于对照组（均P<0.05），而SLC6A14表达水平高于对照组（P<0.05）。UC组结肠组织中SLC6A14蛋白表达水平高于对照组（0.45±0.07比0.30±0.01，P=0.019）。DSS组小鼠肠道中基因SLC6A14的mRNA表达水平高于饮水组（1.83±0.90比0.60±0.10，P=0.035）。 结论： UC患者肠道中与脂肪酸氧化和肉碱代谢相关的基因CD36、CPT1A、CPT1B、CPT2、CRAT、CROT、OCTN1和OCTN2的表达水平降低，且同时转运氨基酸和肉碱的基因SLC6A14的表达水平升高。.