Obesity and High-Fat Diet Disrupt Immune Response
high-fat diet impairs neutrophil function, reducing bacterial defense and impairing immune responses in obese mice.
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A new study published in The Journal of Immunology examines how a high-fat diet (HFD) can impair the immune system's ability to respond to infections, specifically through the dysfunction of neutrophils. Neutrophils are among the first immune cells to respond to bacterial or viral threats. Researchers found that male mice fed a high-fat diet to induce obesity had increased neutrophil numbers. However, these neutrophils showed markers of immaturity or aging and had a reduced ability to kill bacteria.
Neutrophils
A type of white blood cell that is one of the first responders to infection, playing a key role in the body's defense against bacteria and viruses.
Obesity and its effects on the immune system
Obesity, affecting 40.3% of American adults, is commonly induced by long-term excessive calorie consumption, particularly through high-fat and high-sugar diets. Obesity has been associated with chronic low-grade inflammation, which contributes to several obesity-related diseases and heightened vulnerability to infections. This connection underscores the importance of understanding the impact of obesity on immune cell function.
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Subscribe for FREEImpairment of neutrophil function
In the study, mice were divided into two groups: one fed a normal diet and the other a high-fat diet. Researchers isolated neutrophils from both the blood and bone marrow of these mice for comparison. Neutrophils from mice on a high-fat diet exhibited altered gene expression linked to fat storage and metabolism, and they were less effective in storing and releasing TNF-alpha, a key immune signaling molecule. When exposed to Pseudomonas aeruginosa, a bacterium that can cause pneumonia, neutrophils from high-fat diet mice showed significantly impaired bacterial ingestion and killing.
TNF-alpha
A cytokine (immune signaling molecule) involved in systemic inflammation, crucial for regulating immune responses during infections.
Pseudomonas aeruginosa
A bacterium that can cause infections, particularly in the lungs, and is known to be resistant to many common antibiotics.
Future research directions
The findings highlight how diet-induced obesity can compromise neutrophil function, which is crucial for combating infections. The researchers plan to investigate the underlying mechanisms of neutrophil dysfunction, particularly why these cells are defective in their bacterial killing abilities. Future studies will explore whether this dysfunction is specific to certain bacteria or affects a broader range of pathogens.
Reference: Bowers E, Entrup GP, Islam M, et al. High fat diet feeding impairs neutrophil phagocytosis, bacterial killing, and neutrophil-induced hematopoietic regeneration. J Immunol. 2025:vkaf024. doi: 10.1093/jimmun/vkaf024
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