A recent study examined the role of diacylglycerol O-acyltransferases 1 and 2 in obesity-associated colorectal cancer progression.

In the study, published in Gastroenterology, researchers, led by Jenisha Ghimire, of the Department of Pathology and Laboratory Medicine at the Tulane University School of Medicine, investigated the significance of diacylglycerol O-acyltransferases 1 and 2 (DGAT1/2), which drive lipid droplet (LD) biogenesis, in facilitating tumor growth.

The study analyzed human colorectal cancer samples, cell lines, and an Apc^Min/+ mouse model subjected to a high-fat diet.

Among the key findings were:

• Elevated DGAT1/2 Levels: DGAT1/2 levels increased with disease severity and obesity in human colorectal cancer tissue.
• Fatty Acid Influence: DGAT1/2 expression further increased in human colorectal cancer cells upon exposure to fatty acids prevalent in obesity.
• MYC Dependency: DGAT2 upregulation was MYC-dependent.
• Inhibition Effects: DGAT1/2 inhibition improved FOXO3 activity, attenuated the PI3K pathway, reduced MYC-dependent DGAT2 expression and LD accumulation, and induced FOXO3/p27kip1-mediated cell cycle arrest.
• In Vivo Results: DGAT1/2 inhibition reduced colonic tumors in Apc^Min/+ mice on a high-fat diet.

Transcriptomic analysis revealed that DGAT1/2 inhibition targeted metabolic and tumorigenic pathways, stratifying cancerous from normal tissue and predicting advanced disease-free state and survival in patients with colorectal cancer.

"This is a novel mechanism of DGAT1/2-dependent metabolic and tumorigenic remodeling in obesity-facilitated colorectal cancer, providing a platform for future development of effective treatments for patients with colorectal cancer," Ghimire said. 

Further analysis indicated that this inhibition may be predictive of advanced disease-free state and survival in patients with colorectal cancer.

No conflicts of interest were mentioned in the study.