Immune System Signals May Slow Fat Burning
New research suggests immune cells actively regulate how quickly the body releases stored fat during stress, with implications for obesity and metabolic disease.
A Nature study finds that neutrophils release inflammatory signals that slow fat breakdown during cold exposure or fasting, revealing an immune-driven brake on energy expenditure that may contribute to obesity and insulin resistance.
Study Details
The immune system is best known for fighting infections, but new research suggests it also plays a role in regulating metabolism. Investigators at the University of California San Diego School of Medicine examined how the body prevents excessive fat loss during periods of stress such as cold exposure or starvation.
While prior research has focused on how immune cells respond to overeating and obesity, far less is known about how the immune system behaves when the body is actively breaking down fat. The researchers aimed to understand whether immune signaling helps regulate this process to prevent metabolic harm.
The study was published in Nature
Methodology
Using mouse models, researchers pharmacologically activated beta-adrenergic signaling, mimicking the effects of cold exposure and sympathetic nervous system activation.
They then tracked immune cell movement and signaling within adipose tissue, particularly visceral fat surrounding internal organs. The team measured immune cell infiltration, inflammatory signaling, and changes in lipolysis, the process by which fat cells release stored energy.
Key Findings
Neutrophils rapidly migrated into visceral fat within hours of fat cell activation
These neutrophils released interleukin-1-beta (IL-1β), an inflammatory signaling molecule
IL-1β directly suppressed lipolysis, slowing the release of stored fat
Neutrophil recruitment depended on lipolysis itself, forming a feedback loop
The mechanism appeared strongest in visceral fat rather than subcutaneous fat
Implications for Practice
For patients
This research may help explain why sustained weight loss is difficult, especially during dieting or metabolic stress. Even when the body is primed to burn fat, immune signaling may actively slow the process to protect energy reserves. What once helped humans survive famine may now work against weight loss efforts in an environment of constant food availability.
For clinicians
The findings suggest immune-metabolic crosstalk may contribute to insulin resistance and chronic inflammation in obesity. Elevated baseline lipolysis in obesity could drive neutrophil recruitment, worsening inflammatory signaling and metabolic dysfunction over time.
The study also identifies IL-1β and upstream enzymes such as caspase-1 and inflammasome components as potential therapeutic targets. However, complete suppression of these pathways could increase infection risk, highlighting the need for partial or targeted modulation rather than full inhibition.
Combination approaches pairing appetite suppression, such as GLP-1 receptor agonists, with therapies that modestly increase energy expenditure may warrant future investigation.
A More Nuanced View of Fat Tissue
Experts not involved in the study cautioned against viewing inflammation as purely harmful. Adipose tissue plays a critical protective role, and unchecked fat breakdown can overwhelm the liver and lead to fatty liver disease.
Too little fat storage, as seen in lipodystrophy, is also associated with severe metabolic complications. The immune system’s braking mechanism may therefore serve an important protective function, even as it complicates obesity treatment.