January 29, 2026, 9:59 am | Read time: 7 minutes
Did you know that your diet plays a major role in the performance of your immune system? If you want to reduce your susceptibility to cold or flu pathogens, you can achieve a lot with a balanced diet. What should definitely not end up on your plate: fatty foods. These are not good for the immune system. A recent study now explains why this is the case in more detail.
The new study by the University of Michigan shows that a long-term high-fat diet can significantly weaken important immune cells—so-called neutrophil granulocytes. As a result, the body not only becomes more susceptible to infections, but is also less able to recover from health problems. But how exactly does fat unbalance the immune system—and what do inflammation and immune cells have to do with it?
Overview
Study Investigates Immune Cells
To investigate these questions, the research team carried out a series of complex animal experiments. Over 16 weeks, laboratory mice were fed either a normal or a high-fat diet. The researchers then analyzed certain immune cells—known as neutrophils—using specific methods such as single-cell RNA sequencing, metabolic analysis, and cell transplantation.1
What Are Neutrophils?
Neutrophils belong to the white blood cells and play a central role in defending against infections and supporting healing processes in the body. Their number can increase under various circumstances or in certain diseases, for example, in the case of:
- Injuries
- infections
- Inflammatory diseases
- Taking certain medications
- Certain forms of leukemia
Most commonly, an increase in neutrophils occurs as a normal reaction of the body to an infection. If the neutrophil count is elevated, in many cases, this is a sensible defense reaction to promote healing processes or to combat invading pathogens and foreign substances. Infections caused by bacteria, viruses, fungi, or parasites can trigger this increase in the blood.2
What Was Investigated and Why?
Obesity has long been suspected of impairing the immune system, among other things, through permanent, underlying inflammation in the body. Certain inflammatory messengers are elevated in the blood, such as IL-6 or TNF-α. At the same time, the number of certain immune cells, such as monocytes, macrophages, and neutrophils, increases. While much is already known about the role of monocytes and macrophages, the effects on neutrophils have hardly been researched to date.3,4
This is precisely where the current study comes in: The researchers wanted to find out whether a long-term high-fat diet changes the function of these immune cells—for example, their ability to fight bacteria or support bone marrow regeneration.
Course of the Study
Male C57BL/6J mice were fed either a normal diet (13.5 percent fat) or a high-fat diet (60 percent fat) for 16 weeks from the sixth week of life. So-called C57BL/6 mice are among the most widely used inbred lines in biomedical research. As the animals within a strain are genetically identical, test results can be reliably compared—without being influenced by genetic differences. Typical of inbred strains is the great uniformity in hereditary characteristics such as appearance, behavior, and reaction to experimental interventions.5
The research team analyzed individual immune cells for their gene activity, investigated their metabolic processes, tested their ability to defend themselves against bacteria, and carried out cell transplants. The storage of fats in the cells was also visualized.
Use of Inhibitors
The researchers also used certain inhibitors: With C75, they blocked fatty acid synthase (FAS)—an enzyme that produces new fatty acids in the cell. They used etomoxir to inhibit carnitine palmitoyltransferase 1a (CPT1a). This enzyme ensures that fatty acids enter the mitochondria, where they are burned to produce energy. The effect of palmitate—a saturated fatty acid typically found in animal fats—was also tested.
This Is the Result of the Study
The study revealed that a 16-week high-fat diet in mice resulted in a significant expansion of both immature and aged neutrophils in the bone marrow, compromising their functionality. Specifically, the findings included:
Reduced Immune Function
Neutrophils from HFD mice (“high-fat diet”), which were fed a high-fat diet, showed a significantly reduced ability to transport and kill Pseudomonas aeruginosa. The latter is a pathogenic bacterium that can be particularly dangerous for people with a weakened immune system. It is often found in hospitals, is resistant to many antibiotics, and can cause pneumonia, urinary tract infections, or wound infections, for example.6
Another observation: The formation of so-called NETs (neutrophil extracellular traps) was reduced under HFD conditions and after the addition of palmitate. NETs are net-like structures that are formed by activated neutrophils. They consist of DNA and antibodies and serve to trap pathogens and render them harmless.7
Metabolic Shift
In mice fed a diet consisting of 60 percent fat, the immune cells (neutrophils) showed increased activity of genes involved in the handling and storage of fatty acids—particularly Acot1, Cpt1a, and Plin2. This indicates that the cells are increasingly using fatty acids instead of sugar (glucose) as an energy source.
Altered TNF-ɑ Production
At rest, the neutrophils of HFD mice released a significantly lower amount of the inflammatory messenger TNF-ɑ. However, when they were activated by a stimulus (LPS), they reacted with a stronger TNF-ɑ release than normal cells. This effect could be significantly slowed down if certain metabolic pathways for fatty acids were specifically blocked—for example, by inhibiting the enzymes FAS or CPT1a.
Impaired Bone Marrow Regeneration
In a model for bone marrow transplantation, neutrophils from normally nourished mice (ND mice) significantly improved regeneration compared to those from HFD mice. This was probably due to the lower TNF-ɑ release and the altered composition of the cells.
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What Is the Significance of the Results?
The study provides new insights into the extent to which a high-fat environment can influence the metabolism and functioning of neutrophils. Although the number of these white blood cells increases under a high-fat diet, their performance deteriorates significantly.
This means that being overweight (due to a high-fat diet) can not only promote chronic diseases, but also increase the risk of infection. The results also suggest that the body may recover less well after medical stress (simulated in the bone marrow transplant model), such as chemotherapy, because important immune cells lose their supporting function in the bone marrow.
Discussion and Limitations
The study impresses with a broad selection of modern examination methods and a very precise analysis at the cell level. Particularly noteworthy is the single-cell sequencing, with which different types of neutrophils could be precisely described.
However, there are also limitations. The experiments were carried out on laboratory animals, and further research is needed to determine how exactly the results can be transferred to humans. In addition, the researchers only included male mice in their experiments, although immune reactions may be different in female animals. In addition, only the bone marrow was examined—neutrophils could react differently in other tissues. Also worth noting: The researchers did not specifically investigate the role of the messenger TNF-ɑ by gene silencing (knockout). It therefore remains unclear whether it is actually responsible for the observed effects.
Conclusions
The study indicates that a high-fat diet can significantly weaken the body’s defenses, primarily due to alterations in cellular metabolism. The study presented suggests that a high fat content in the diet not only increases the risk of infection, but also makes regeneration after exercise more difficult. The findings provide new starting points on how to specifically support the immune system in the event of metabolic disorders.
The German original of this article was published in March 2025.