Leptin, Nesfatin-1, Glucagon-like Peptide 1, and Short-Chain Fatty Acids in Colon Cancer and Inflammatory Bowel Disease

Abstract

Background: Short-chain fatty acids (SCFAs) are produced by the colon microbiome and bind to specific G-protein coupled receptors GPR 41 and GPR 43. Leptin and glucagon-like peptide 1 (GLP-1) are produced mainly in the intestinal lumen as a result of SCFAs binding to their receptors at this level. Inflammatory bowel diseases (IBD) such as Crohn’s disease (CD) and ulcerative colitis (UC), and their major complication, colorectal cancer (CRC), can disturb the dynamics of the colonic microenvironment thus influencing SCFAs production and effects. Our study aimed to investigate serum levels of SCFAs and SCFAs-mediated production of circulating leptin, GLP-1, and Nesfatin-1 in patients with IBD and CRC. Methods: A total of 88 subjects (29 with CRC, 29 with IBD, and 30 controls) were included in this pilot study. Serum SCFAs, leptin, Nesfatin-1, and GLP-1 levels were analyzed. Results: Nesfatin-1 levels were significantly higher in CRC patients (p < 0.05) compared to IBD and controls. Leptin levels were positively correlated with Nesfatin-1 levels in CRC, IBD, and control groups (CRC: R2 = 0.6585, p < 0.01; IBD: R2 = 0.2984, p < 0.01; Control: R2 = 0.2087, p < 0.05). Serum SCFAs levels were negatively correlated with GLP-1 levels in CRC and IBD (CRC: R2 = 0.3324, p < 0.01; IBD: R2 = 0.1756, p < 0.05) and negatively correlated with Nesfatin-1 levels in CRC (R2 = 0.2375, p < 0.05). Conclusions: These findings suggest that alterations in gut microenvironment may influence systemic metabolic regulators involved in appetite control and inflammation, potentially influencing IBD and CRC pathogenesis. This is the first study to evaluate the relationships between Nesfatin-1, leptin, GLP-1, and SCFAs in CRC and IBD patients; further research is needed to clarify their mechanistic links and therapeutic potential.