Role of Fat Metabolism in Colon Cancer Development

Colorectal cancer, like many diseases, is influenced by various factors, and a recent focus has been on the balance between pro-inflammatory and resolving mediators. This balance is crucial, as an overproduction of pro-inflammatory mediators, such as leukotrienes created from arachidonic acid, is observed in colorectal cancer, while inflammation-resolving mediators are nearly nonexistent.

Researchers are seeking to identify the specific mechanisms that sustain chronic inflammation in colorectal cancer. By doing so, they can develop targeted interventions to disrupt these pathways, potentially improving colorectal cancer outcomes.

The integration of lipidomics with single cell and spatial transcriptomics has defined an unresolved pro-inflammatory state in colon cancer. This integration offers a powerful tool for understanding the role of lipid metabolism in colorectal cancer.

Tumor-associated macrophages (TAMs) are identified as key contributors to the inflammatory lipid profile in colorectal cancer. Arachidonate 5-lipoxygenase (ALOX5), an enzyme responsible for producing leukotrienes, is highly expressed in TAMs in colorectal cancer. Spatial transcriptomics showed the co-localization of pro-inflammatory enzymes and lipid mediators with immune and stromal cells in the tumor microenvironment, suggesting that the inflammatory state is an integral component of tumor progression in colorectal cancer.

Inflammation in colorectal cancer is typically regulated through a process called lipid mediator class switching, which involves a transition from pro-inflammatory to inflammation-resolving lipid molecules. However, a study revealed a reduction in the expression of enzymes involved in the synthesis of resolving mediators, such as arachidonate 15-lipoxygenase (ALOX15), in colorectal cancer.

Omega-3 fatty acids, found in foods such as fish and flaxseed, are precursors to resolving mediators and may help balance the metabolic disruptions observed in colorectal cancer. Western diets, rich in omega-6 fatty acids, are linked to the elevated production of pro-inflammatory lipids in colorectal cancer.

Inhibiting ALOX5 or enhancing the activity of ALOX15 could shift the lipid mediator profile toward resolution in colorectal cancer. Specialized pro-resolving mediators (SPMs), derived from omega-3 fatty acids, can help restore this balance. SPMs have been found to reduce the chronic inflammatory state that supports tumor growth in colorectal cancer.

While the specific researcher or research group that published the study on the role of lipid metabolism disorders in chronic inflammation and colorectal cancer progression is not identified in the provided search results, the integration of lipidomics with advanced molecular techniques offers promising avenues for future research in this field.