Neutrophils preserve energy storage in sympathetically activated adipocytes
Summary
Article Date: 10 December 2025
Article URL: https://www.nature.com/articles/s41586-025-09839-6
Article Image: https://www.nature.com/articles/s41586-025-09839-6
This Nature study shows that brief sympathetic activation of white adipose tissue (by β3-adrenergic agonist CL-316,243 or cold exposure) triggers lipolysis and rapidly recruits neutrophils into adipose tissue. Those neutrophils produce Interleukin-1β (IL-1β), which induces catecholamine resistance in adipocytes and thereby suppresses excessive lipolysis. The recruitment depends on lipolysis-driven leukotriene B4 (LTB4) and a p38 signalling axis. Depleting neutrophils or blocking IL-1β/inflammasome activity increases lipolysis and energy loss. Human adipose transcriptomic data show inflammasome/IL-1 pathway genes correlate with obesity-related traits, linking the mechanism to metabolic disease contexts.
Key Points
- Sympathetic stimulation (CL-316,243 or cold) rapidly recruits neutrophils to white adipose tissue.
- Adipocyte lipolysis generates LTB4 via a p38-dependent pathway that attracts neutrophils.
- Infiltrating neutrophils are a major local source of IL-1β in adipose tissue following activation.
- Neutrophil-derived IL-1β induces catecholamine resistance in adipocytes, restraining lipolysis and limiting energy loss.
- Removing neutrophils or inhibiting IL-1β/executioner inflammasome components increases lipolysis and tissue energy depletion.
- Human adipose data show higher inflammasome/IL-1 expression in obesity, suggesting clinical relevance to metabolic disease and energy homeostasis.
Context and relevance
This work sits at the intersection of immunology and metabolism: it reframes neutrophils not just as pro-inflammatory actors but as acute regulators that protect whole-body energy stores during sympathetic challenge. The pathway (lipolysis → LTB4 → neutrophil recruitment → IL-1β → adipocyte catecholamine resistance) provides mechanistic detail linking short-term sympathetic activation to controlled lipolytic response. That has potential implications for therapies aiming to manipulate thermogenesis, lipolysis or inflammation in obesity and metabolic disease.
Author style
Punchy: the paper identifies a fast, adaptive immune check on fat breakdown — neutrophils dial back lipolysis so you don’t burn through reserves too fast. If you care about immunometabolism or therapeutic ways to modulate fat mobilisation, this one matters.
Why should I read this?
Short and informal: want to know how immune cells stop you from wasting away when your sympathetic nervous system screams ‘burn fat’? These authors did the heavy lifting and show neutrophils swoop in, spit out IL-1β and blunt adrenergic lipolysis. It’s neat, unexpected and important if you’re following obesity, thermogenesis or inflammation — plus it points to new druggable nodes (LTB4, inflammasome/IL-1β) for tweaking energy balance.