Our immune cells actively ensure that we don’t lose weight too quickly. During metabolic stress, they migrate into the fatty tissue and slow down fat breakdown with the help of signaling molecules. This is shown by a study based on experiments with mice. If the researchers blocked the corresponding signaling pathway in their test animals, they lost their fat deposits more quickly. The responsible genes are also particularly active in overweight people. The findings offer a new approach to developing more effective treatments for obesity.
Obese people often find it particularly difficult to lose weight. Even fasting cures and strict diets often do not have the desired effect. Exercise is also usually less effective at burning calories in people who are very overweight. This is due to various processes in our body that together ensure that we do not lose the pounds that we have accumulated so quickly – including changes in the brain, in the intestinal flora and in the fat cells themselves.
Immune protection for fat deposits
A team led by Seunghwan Son from the University of California in San Diego has now discovered another mechanism by which our body holds on to the extra kilos: with the help of the immune system. A group of white blood cells called neutrophils is responsible. “Neutrophils are the first line of defense during infections, but our study shows that they also play a role in metabolic stress,” report the researchers. Metabolic stress occurs, among other things, when we eat too little food or when our body is exposed to cold. In response, the sympathetic nervous system – the part of the autonomic nervous system responsible for stress responses – is activated and ensures that we release our energy reserves stored in fatty tissue.
“While fat burning is essential for short-term metabolic adaptation, sustained metabolic stress requires adaptive changes that maintain energy reserves,” explains the research team. This is where the neutrophils come into play: As Son and his colleagues have shown in experiments on mice, the immune cells migrate into the fatty tissue in response to sympathetic activation and, with the help of molecular messenger substances, activate a signaling chain that slows down fat burning. Neutrophils are particularly active in the visceral white fatty tissue that surrounds our internal organs. Abdominal fat, which is considered particularly harmful to health, melts the slowest.
When the researchers paralyzed the neutrophils in mice, significantly fewer of the fat-protecting signal molecules were found in the fatty tissue of the test animals and fat breakdown was not slowed down. The same effect was also seen when the team blocked the relevant signaling molecules, particularly the inflammatory messenger interleukin-1-beta. “Taken together, these results show that interleukin-1 beta released by neutrophils is involved in maintaining fat stores during metabolic stress,” the researchers conclude.
Approaches for new obesity treatments
Further research revealed that the genes involved in this signaling pathway are particularly active in overweight people. This suggests that these people’s immune systems are particularly good at inhibiting fat loss. This could also be a starting point for new therapies against obesity. While it was evolutionarily important for our ancestors not to lose weight too quickly even in times of food shortage, many obese people today want to lose weight quickly. If the newly discovered signaling pathway can be influenced with medication without serious side effects, it could become easier to lose the extra pounds.
Source: Seunghwan Son (University of California, San Diego) et al., Nature, doi: 10.10384/s41586-025-09839-6