[Changes in the expression of genes related to intestinal fatty acid oxidation and carnitine metabolism in patients with ulcerative colitis].

Abstract

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.