Omentin-1 ameliorates experimental inflammatory bowel disease via Nrf2 activation and redox regulation

• Published in: Life sciences (1973) Vol. 328; p. 121847
• Main Authors: Tao, Meihui, Yan, Wei, Chen, Chaoyue, Tang, Mengfan, Zhao, Xi, Feng, Qinyu, Fei, Xiaoshang, Fu, Yu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.09.2023
• Subjects: Acute colitis; Intestinal barrier function; NF-κB pathways; Nrf2 signaling; Omentin-1; Redox regulation; CD; NQO-1; DSS; Intestinal barrier function; Redox regulation; GST; SOD; HO-1; IBD; Omentin-1; IQR; MDA; DAI; Nrf2 signaling; UC; NF-κB pathways; CCK8; Nrf2; FD4; Keap1; SES-CD; Acute colitis
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2023.121847

Omentin-1 production is decreased in patients with IBD. However, the specific role of Omentin-1 in IBD has not been fully elucidated. This study aimed to investigate the expression and role of Omentin-1 in IBD and the potential mechanisms. We collected human serum and colon biopsy samples at the Wuhan Union Hospital. Omentin-1 recombinant protein was injected intraperitoneally in a DSS-induced experimental IBD mouse model. Omentin-1 levels were measured in IBD patients, colitis mice, and LPS-induced HT-29 cells. Omentin-1 and/or a Nrf2 specific inhibitor (ML385) were administered to DSS mice and LPS-induced HT-29 cells. The effects of Omentin-1 on inflammation, intestinal barrier function, Nrf2 pathway, oxidative stress, and NF-κB signaling were detected in vivo and in vitro. Serum Omentin-1 levels were significantly reduced in UC and CD patients compared with controls (173.7 (IQR, 120.1–221.2) ng/ml, 80.8 (43.8–151.8) ng/ml, and 270.7 (220.7–306.5) ng/ml, respectively). The levels of Omentin-1 were also significantly lower in colitis mice and LPS-induced HT-29 cells. Omentin-1 treatment effectively ameliorated inflammation and impaired intestinal barrier, decreased ROS and MDA levels, and increased GSH and SOD production in the DSS-induced colitis mice and LPS-induced HT-29 cells. Mechanically, Omentin-1 repaired the intestinal barrier by activating Nrf2, then improving oxidative stress and inhibiting NF-κB signaling. Furthermore, the interaction between Omentin-1 and Nrf2 was identified. Omentin-1 activates the Nrf2 pathway to regulate redox balance, ultimately protecting intestinal barrier function and reducing intestinal inflammation. In general, Omentin-1 can be used as a promising therapeutic target for IBD.