NK cell battling a tumor cell, its machinery clogged by fat.

Fat's Hidden Role: How Obesity Impacts Your Immune System's Cancer-Fighting Abilities

Author's portrait.
Elliot Brynn in Health & Wellness August 2025 • 4 min read.

"New research reveals how excess fat can sabotage the vital work of natural killer cells, hindering their ability to destroy tumor cells and potentially opening doors for new cancer immunotherapies."


Obesity is a significant risk factor for several diseases, including cancer. Recent studies suggest that obesity can disrupt the immune system, weakening the body's ability to fight off tumors. While the immune system usually protects against the establishment and spread of cancer, the specific ways obesity interferes with this protection have been unclear.

Now, researchers led by Lydia Lynch have uncovered a critical mechanism: in obese individuals, lipids (fats) can accumulate within natural killer (NK) cells. These NK cells are a type of immune cell crucial for destroying infected or cancerous cells. The accumulation of fat impairs their ability to move to the site of contact with tumor cells, crippling their ability to kill them.

This article will delve into the details of this groundbreaking research, explaining how excess fat clogs up the machinery within NK cells, preventing them from functioning correctly. We'll explore the implications of these findings for cancer prevention and treatment, offering insights into potential new therapies that could restore immune function in obese individuals.

How Fat Blocks Natural Killer Cells: The Cytotoxic Machinery Breakdown

NK cell battling a tumor cell, its machinery clogged by fat.

The researchers discovered that in obese individuals, NK cells undergo metabolic changes that interfere with their cancer-fighting abilities. Specifically, the NK cells from obese mice and humans showed increased lipid handling and metabolism. This excess fat accumulation directly correlated with a decrease in their cytotoxicity – their ability to kill target cells.

Using advanced imaging techniques, the researchers observed that while free fatty acid treatment didn't prevent NK cells from recognizing tumor cells, it did block a crucial step: the intracellular movement of lytic granules. These granules contain powerful enzymes that NK cells use to destroy cancer cells. The fat accumulation essentially jammed the gears, preventing the granules from reaching their target.

  • Fat Accumulation: Lipids build up inside NK cells.
  • Movement Blocked: Lytic granules can't reach tumor cells.
  • Killing Impaired: NK cells fail to destroy cancer cells effectively.
Interestingly, when the researchers blocked fatty acids from entering the mitochondria (the cell's power plants), they saw a reversal of the effect. Glycolysis, a different metabolic pathway, was boosted, and NK cell cytotoxicity was restored. This suggests that the problem wasn't simply the presence of fat, but the way it was being processed within the cell.

Future Implications: Reclaiming Your Immune System's Cancer-Fighting Power

This research marks a significant step forward in understanding how obesity impacts immune function and cancer risk. The findings suggest that metabolic reprogramming of NK cells plays a crucial role in the reduced ability to fight tumors in obese individuals. As Lydia Lynch states, "We show for the first time that metabolic reprogramming of NK cells in obesity leads to NK cell defects and reduced tumor killing."

The study opens exciting possibilities for future cancer immunotherapies. By targeting lipid metabolism in NK cells, researchers hope to develop strategies to restore their cytotoxic function and enhance the body's natural defenses against cancer. This could involve blocking lipid uptake or altering lipid metabolism within these immune cells.

Ultimately, these findings highlight the importance of maintaining a healthy weight and lifestyle for optimal immune function. While further research is needed, this study provides a compelling link between obesity, immune dysfunction, and cancer, paving the way for new approaches to cancer prevention and treatment.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

1

How does obesity affect the ability of natural killer cells to fight cancer?

In individuals with obesity, lipids accumulate within natural killer cells. This accumulation impairs their ability to move to the site of contact with tumor cells, crippling their ability to effectively destroy those cancerous cells. This interference with the normal function of natural killer cells is linked to metabolic changes within the cell.

2

What is the role of lytic granules in the cancer-fighting process of natural killer cells, and how does fat accumulation interfere with this process?

Natural killer cells use lytic granules, which contain powerful enzymes, to destroy cancer cells. In obese individuals, the accumulation of fat blocks the intracellular movement of these lytic granules. As a result, although natural killer cells can still recognize tumor cells, they cannot deliver the enzymes necessary to kill them.

3

What happened when researchers blocked fatty acids from entering the mitochondria of natural killer cells, and what does this suggest about the impact of fat on immune function?

Researchers found that by blocking fatty acids from entering the mitochondria within natural killer cells, they could reverse the negative effects of fat accumulation. This blockage boosted glycolysis, a different metabolic pathway, and restored natural killer cell cytotoxicity. This indicates that it is not just the presence of fat, but also how it is being processed within the cell, that impacts the immune function.

4

What are the potential future implications of this research for cancer prevention and treatment?

This research suggests that metabolic reprogramming of natural killer cells plays a crucial role in the reduced ability to fight tumors in individuals with obesity. By understanding the mechanisms of how fat accumulation affects the cells, scientists can explore new therapeutic strategies to restore immune function. These strategies could potentially involve targeting metabolic pathways within natural killer cells to enhance their ability to eliminate cancer cells.

5

How does this research highlight the connection between metabolism, immune function, and cancer risk, and what actions can be taken to support the optimal function of natural killer cells?

This research emphasizes the importance of maintaining a healthy metabolism to support the optimal function of the immune system. By preventing excess fat accumulation and promoting healthy metabolic processes, it may be possible to enhance the cancer-fighting abilities of natural killer cells and reduce the risk of cancer. Future studies may focus on developing personalized strategies to optimize natural killer cell metabolism based on an individual's specific metabolic profile.

Newsletter Subscribe

Subscribe to get the latest articles and insights directly in your inbox.