Differential Effects of Saturated and Unsaturated Fatty Acids on Colorectal Cancer via IDO1 Signaling

Colorectal cancer (CRC) incidence has risen significantly in China, potentially linked to dietary Westernization and increased consumption of high-fat diets (HFD).

This study examines the differential effects of various fatty acids-saturated (palmitic acid, PA), monounsaturated (oleic acid, OA), and polyunsaturated (arachidonic acid, AA; docosahexaenoic acid, DHA)-on CRC progression, focusing on the IDO1/AhR signaling pathway.

Clinical data indicate that CRC patients exhibit elevated serum lipid levels, with PA promoting cell proliferation, migration, and invasion more strongly than unsaturated fatty acids. The pro-tumorigenic effects of PA are enhanced in the presence of lipopolysaccharide (LPS), suggesting an interaction between diet and gut microbiota. In vivo experiments corroborate that a high-PA diet significantly elevates tumor growth and IDO1 expression compared to DHA. Mechanistic analyses reveal that PA and LPS co-stimulation activates the IDO1-AhR-PI3K/Akt-NF-κB pathway, which is implicated in CRC progression.

These findings suggest that saturated fatty acids, particularly PA, may exacerbate CRC development risk through metabolic dysregulation, highlighting the potential of IDO1 as a biomarker for CRC associated with HFD. Reducing dietary saturated fat intake may thus be a viable strategy for CRC prevention.