Surprising new function of immune cells uncovered: Excess weight loss prevention

Researchers at the University of California San Diego School of Medicine have uncovered a surprising new function for immune cells: preventing excess weight loss. In a recent study, the team demonstrates that when the body is exposed to physiological stressors, such as low temperature, neutrophils - a type of white blood cell - infiltrate fat tissue and release signals that slow fat breakdown. The researchers hypothesize that this mechanism helped our early human ancestors preserve vital energy stores when food was scarce or when exposed to prolonged periods of cold. Today, the findings could help yield new approaches to managing obesity and other metabolic disorders.

White adipose tissue (WAT) - commonly known as body fat - plays a vital role in maintaining energy balance by storing excess energy and releasing it as needed during periods of fasting, cold or other metabolic stress. These biochemical processes are carefully managed by the body in order to prevent excessive fat loss, which can be very dangerous. Until now, the mechanisms that protect the body against runaway fat burning in times of stress have remained unclear.

To address this, the researchers studied a combination of mouse models and human genetic data. Key findings include:

• In mouse models, activating the sympathetic nervous system triggered a rapid influx of neutrophils into visceral fat, the fat surrounding vital organs. This neutrophil recruitment depended on both ongoing fat breakdown and activation of specific inflammatory pathways in fat cells.
• Neutrophils arriving in the fat tissue produced signaling molecules that suppressed further fat loss in surrounding tissue.
• When either these molecules or neutrophils themselves were depleted, mice experienced increased fat breakdown under metabolic stress.
• In obese individuals, genes involved with this pathway were more active.

These findings reveal an unexpected physiological partnership between fat cells and immune cells, demonstrating that the immune system is crucial not only for fighting infection but also for maintaining energy balance. The study also provides new insight into the underlying metabolism of obesity and other metabolic disorders. Targeting this newly discovered pathway may eventually offer new strategies for treating obesity, metabolic syndrome or conditions involving unintended weight loss.

The study, published in Nature, was led by Seung Son Hwan, Ph.D., a postdoctoral researcher at UC San Diego, and Alan Saltiel, Ph.D., professor of pharmacology at UC San Diego School of Medicine. The study was supported, in part, by grants from the Larry L. Hillblom Foundation and the National Institutes of Health. The authors declare no competing interests.