High-fat diet and obesity impair key immune functions, new study finds
A recent study published in The Journal of Immunology has shed new light on how a high-fat diet (HFD) and obesity can compromise the immune system’s ability to fight infection. The research focuses on neutrophils—white blood cells that serve as one of the body’s first lines of defence against invading bacteria and viruses—and reveals that exposure to a high-fat diet alters their number, maturity, and function.
The study was led by Dr Kanakadurga Singer, Associate Professor in the Departments of Paediatrics and Molecular & Integrative Physiology at the University of Michigan Medical School. Her team used a widely accepted mouse model to examine the effects of a high-fat diet on immune response. Male mice were fed either a standard diet or a high-fat diet known to induce obesity. The researchers then isolated neutrophils from the animals’ blood and bone marrow to assess their function.
Mice fed the high-fat diet not only had an increased number of neutrophils but also displayed significant changes in the characteristics of these cells. Many of the neutrophils were either immature or aged, and crucially, they showed a diminished ability to kill bacteria.
“When neutrophils were exposed to Pseudomonas aeruginosa, a bacterium known to cause pneumonia, the neutrophils from high-fat diet-fed mice exhibited a significantly reduced capacity to ingest and eliminate the bacteria,” the study reported. This impaired response suggests that individuals with obesity may have weakened early immune defences, increasing their susceptibility to infection.
In addition to compromised bacterial killing, neutrophils from the high-fat diet group demonstrated alterations in gene expression related to fat storage and metabolism. They also showed a reduced ability to store and release tumour necrosis factor-alpha (TNF-α), an important signalling molecule that regulates inflammation and immune responses.
The findings are particularly relevant given the high prevalence of obesity. In the United States, 40.3% of adults are currently living with obesity—a condition that often develops when energy intake consistently exceeds energy expenditure, especially through diets rich in fat and/or sugar. Obesity is increasingly recognised as a state of chronic, low-grade inflammation, which is believed to contribute to the development of various obesity-related conditions, including impaired immunity.
“The link between chronic inflammation and increased infections highlights the importance of understanding how immune cells like neutrophils are affected by obesity,” explained Dr Singer. “We hope that by understanding how neutrophil function is altered with exposure to high-fat diet, we can take future steps to restore function and improve patient health outcomes.”
She added:
“We hope this study lets investigators and clinicians know that although neutrophils may be increased in number in individuals with elevated BMI or diet-induced obesity, these neutrophils may not be functional.”
The study offers important insights into how dietary patterns and weight status can influence immune health. The next step, according to Dr Singer, is to explore the underlying mechanisms driving neutrophil dysfunction in the context of a high-fat diet.
“We hope to build on these findings by uncovering what is causing the impairment of neutrophils exposed to HFD,” she said. “My team plans to conduct further studies on why these neutrophils are defective, especially in their bacterial killing function, and if these neutrophils are impaired in killing specific types of bacteria or a wide range. Hopefully, we can identify other implications of neutrophil dysfunction due to HFD and if there are ways to improve this impaired function.”
This research underscores the complex interplay between nutrition, body weight, and immune function, reinforcing the need for a deeper understanding of how diet-induced obesity affects health at the cellular level.
