Research Reveals Distinct Impacts of Dietary Fats on Tumor Growth in Obese Mice

Recent research conducted by scientists at the Ludwig Institute for Cancer Research has unveiled significant insights into the relationship between dietary fats and tumor growth in obese mice. The study, published in Nature Metabolism, challenges the notion that obesity itself is the primary driver of cancer progression, suggesting instead that the type of dietary fat consumed plays a crucial role.

Obesity is known to increase the risk of various cancers, including breast, colon, and liver cancer. Additionally, it hampers immune responses that are essential for combating tumors, particularly those stimulated by cancer immunotherapies. However, the specific contributions of dietary fats versus general body fat had remained largely unclear until now.

The decade-long investigation led by Lydia Lynch at Ludwig Princeton found that high-fat diets rich in animal fats, such as lard, beef tallow, and butter, significantly compromised anti-tumor immunity and accelerated tumor growth in obese mice. In contrast, diets containing plant-derived fats like coconut oil, palm oil, and olive oil did not exhibit the same detrimental effects, even when the mice were equally obese.

According to the researchers, modifying dietary fat sources may represent a beneficial approach for obese patients undergoing cancer treatment. Such dietary adjustments could also potentially reduce cancer risk among individuals experiencing obesity.

The study's findings build on previous research that demonstrated how obesity alters the immune system and the tumor microenvironment, contributing to tumor development. It has been established that obesity impairs the body's cancer surveillance mechanisms, which in turn affects the infiltration and function of immune cells, particularly cytotoxic T cells (CTLs) and natural killer (NK) cells, within tumors.

In this latest research, the team elucidated the mechanisms by which metabolites derived from animal fats inhibit the function of NK cells and CTLs. They found that this immune dysfunction is a key factor facilitating tumor progression in obese mice--an effect not observed in those fed plant-based diets. Notably, a diet rich in palm oil appeared to enhance anti-tumor immunity and slow tumor growth in the same population of mice.

The researchers identified specific metabolic intermediates of dietary fats, particularly long-chain acylcarnitines, which were found to markedly suppress the activity of NK cells and CTLs. These harmful metabolites were elevated in obese mice fed diets based on animal fats, while those on plant-fat diets did not show the same levels. The study revealed that these metabolites induce severe metabolic impairments in the mitochondria of CTLs, which diminishes their ability to effectively kill tumor cells and produce essential cytokines.

Conversely, the palm oil-based diet prevented metabolic dysfunction in NK cells among obese mice, likely by enhancing the activity of a critical cellular metabolism regulator known as c-Myc. The expression of this regulator was notably reduced in mice consuming animal fats and in NK cells from humans with obesity.

Lynch emphasized the importance of dietary choices in maintaining a robust immune system and indicated that adjustments to fat consumption could lead to improved outcomes for obese cancer patients. The researchers advocate for clinical evaluations of dietary interventions that focus on fat sources for individuals undergoing cancer treatment.

Overall, this research underscores the pivotal role that dietary fats play in cancer biology, particularly in the context of obesity, and highlights the potential for tailored dietary strategies in cancer prevention and management.