Scientists Discover How the Immune System Actively Slows Weight Loss by Protecting Fat Stores
Researchers from the University of California San Diego School of Medicine have uncovered an unexpected and fascinating role played by the immune system in regulating body weight. According to a new study published in Nature, certain immune cells step in during times of physical stress to prevent excessive weight loss by slowing down how quickly the body burns fat.
At the center of this discovery are neutrophils, a type of white blood cell best known for fighting infections. The research shows that these immune cells also act as guardians of the body’s energy reserves, especially when conditions threaten to deplete fat stores too quickly.
A New Role for Immune Cells Beyond Fighting Infection
For years, scientists have known that white adipose tissue (WAT)—commonly referred to as body fat—is more than just a passive energy storage site. It actively releases energy when the body needs it, such as during fasting, exposure to cold, or other forms of metabolic stress. However, what remained unclear was how the body prevents this fat-burning process from going too far.
This new research fills in that gap. The study shows that when the body experiences physiological stress, the sympathetic nervous system—the same system responsible for the “fight or flight” response—becomes activated. This activation normally signals fat cells to begin breaking down stored fat in a process known as lipolysis.
But here’s where the immune system comes in.
How Neutrophils Enter Fat Tissue During Stress
Using a combination of mouse models and human genetic data, the researchers observed that activation of the sympathetic nervous system triggers a rapid influx of neutrophils into visceral fat, which is the fat that surrounds internal organs like the liver and intestines.
This infiltration doesn’t happen randomly. The recruitment of neutrophils depends on two key factors:
- Ongoing fat breakdown within the tissue
- Activation of specific inflammatory pathways inside fat cells themselves
In other words, fat cells undergoing stress send out signals that attract neutrophils. Once these immune cells arrive, they begin to change the local environment inside the fat tissue.
Neutrophils Act as a Brake on Fat Breakdown
Once inside visceral fat, neutrophils release signaling molecules that directly suppress further fat breakdown in surrounding adipose tissue. These signals effectively act as a biological brake, preventing lipolysis from continuing unchecked.
The study showed that when neutrophils were depleted—or when their signaling molecules were blocked—mice experienced significantly increased fat breakdown during metabolic stress. Without neutrophils present, fat loss accelerated beyond normal levels.
This finding demonstrates a clear and previously unknown physiological partnership between immune cells and fat cells, revealing that the immune system plays an active role in maintaining energy balance.
Why Preventing Excessive Fat Loss Matters
While weight loss is often viewed positively, too much fat loss too quickly can be dangerous. Fat tissue provides essential energy reserves that help the body survive during prolonged periods without food or during harsh environmental conditions.
The researchers believe this immune-driven mechanism likely evolved as a survival advantage for early humans. During times of food scarcity or prolonged cold exposure, preserving fat stores would have been critical for survival. Neutrophils stepping in to slow fat loss may have helped prevent starvation and energy collapse.
In today’s world, however, where food is abundant and lifestyles are often sedentary, this same protective mechanism may contribute to difficulty losing weight, especially in people with obesity.
Evidence from Human Genetic Data
To understand whether this mechanism is relevant in humans, the research team analyzed human genetic datasets. They found that in obese individuals, genes involved in this neutrophil-related pathway were more active.
This suggests that the immune system’s role in protecting fat stores is not limited to laboratory animals but also operates in people. It may help explain why some individuals experience resistance to weight loss, even when exposed to conditions that normally promote fat burning.
Implications for Obesity and Metabolic Disorders
These findings provide new insight into the underlying biology of obesity and metabolic disorders. Traditionally, weight regulation has been framed around diet, exercise, hormones, and genetics. This study adds another crucial layer: immune system involvement.
By identifying a pathway where immune cells actively suppress fat breakdown, the research opens the door to potential new therapeutic strategies. Targeting this immune–fat interaction could one day help:
- Improve treatments for obesity
- Address metabolic syndrome
- Prevent harmful weight loss in conditions involving chronic illness or malnutrition
However, researchers caution that neutrophils and their signaling molecules play essential roles in inflammation and immune defense. Any future therapies would need to carefully balance metabolic benefits with immune health.
The Broader Science of Fat and Immune System Interaction
This study fits into a growing body of research showing that fat tissue is deeply connected to the immune system. Adipose tissue contains many immune cells, including macrophages, T cells, and now clearly neutrophils, all of which influence metabolism.
Fat tissue doesn’t just store energy—it actively communicates with the brain, hormones, and immune system to regulate hunger, energy use, and inflammation. Disruptions in this communication are increasingly linked to metabolic diseases.
Why This Discovery Matters
What makes this study particularly important is that it challenges the idea that fat loss is controlled solely by calorie balance and hormones. Instead, it shows that the body has built-in immune safeguards designed to protect energy reserves under stress.
This helps explain why weight loss is often more complex—and more difficult—than it appears on the surface. The immune system, acting with good evolutionary intentions, may sometimes work against modern weight-loss goals.
Final Thoughts
The discovery that neutrophils actively preserve fat during stress reshapes our understanding of how the body regulates weight. It highlights the immune system as a key player in metabolism and opens new avenues for research into obesity, energy balance, and metabolic health.
As scientists continue to unravel the complex relationship between fat cells and immune cells, future treatments may become more precise, addressing not just calories and exercise, but also the immune signals that quietly shape how our bodies store and burn energy.
Research paper:
https://doi.org/10.1038/s41586-025-09839-6
