A new study by Portland State University researchers is the first to show that eating a diet exclusively high in saturated fats can reprogram the mouse immune system, making it better able to fight off infection but more susceptible to systemic inflammatory conditions, including sepsis. Brooke Napier, assistant professor of biology at PSU, led the study, which was published in eLife.
The ketogenic or “keto” diet is a popular high-fat diet used for weight loss or to control epileptic seizures. This study shows that when mice eat a ketogenic diet that is high in saturated fats it can have a significant impact on their immune system.
A previous study by Napier and colleagues found that mice fed a high-fat, high-sugar Western diet were more susceptible to sepsis and had a higher mortality rate than mice fed a standard diet. In the current study, the researchers found similar effects in mice fed a high-fat ketogenic diet, suggesting that dietary fat may play a role in sepsis.
The researchers focused on one particular fat found in the blood of the mice fed a ketogenic diet: palmitic acid, which is commonly found in animal fats and dairy products. Remarkably, mice fed a normal diet who were injected with palmitic acid also became more susceptible to sepsis.
“It was just exposure to this one saturated fat that made them more susceptible to sepsis mortality,” says Napier. “The idea that you could have a specific fat in your diet that would cause such a drastic outcome in disease is kind of incredible.”
Napier and her team next probed just how exactly high levels of palmitic acid could initiate sepsis. Their first clue came when they noticed that mice fed the Western diet, mice fed the ketogenic diet, and mice treated with palmitic acid all had high levels of inflammatory cytokines, immunological hormones that can cause fever and systemic inflammation during sepsis.
The presence of the inflammatory cytokines suggested that palmitic acid could be affecting the immune system by causing inflammation, but Napier soon discovered that the story was more complicated — and more interesting — than that.
A double-edged sword
The mammalian immune…