Pharmacy Researchers Identify New Avenue in which Free-fatty Acid Receptor-4 Reduces Inflammation


College of Pharmacy researchers have identified a new avenue in which the omega-3 fatty acid receptor known as free-fatty acid receptor-4, or FFA4, reduces inflammation. Their study, led by Nader Moniri, associate dean for research in the College, is published today in Biochemical Pharmacology and funded by the National Institutes of Health.

Activating FFA4 either by omega-3 fatty acids or by synthetic small molecule drugs reduces inflammatory signals from immune cells known as macrophages. Macrophages are a type of white blood cell that form in response to infection or other types of cell and tissue damage, but if they are present for an extended period of time, they can instead promote inflammation. Chronic inflammation can lead to insulin resistance and type 2 diabetes, among other diseases, but drugs that activate FFA4 in macrophages have been shown to reverse insulin resistance and promote anti-diabetic effects.

The Moniri research group found that drugs that activate FFA4 in macrophages also produce a significant reduction in reactive oxygen species, or ROS. ROS are natural byproducts of oxygen metabolism, but high levels can cause inflammation and oxidative stress. In macrophages, ROS can convert beneficial anti-inflammatory cells to harmful inflammation-causing ones.  

The same drugs that reduced ROS also diminished the inflammatory action of cyclooxygenase-2, or COX-2, an enzyme that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen target, the researchers found. Omega-3 fatty acids are known to reduce both ROS and COX-2 enzymes.  

“The finding that activating FFA4 can reduce ROS adds to the known inflammation-modulating properties of this receptor,” Moniri said. “Activating FFA4 also suggests that drugs that activate this receptor can alleviate inflammation through many different cellular mechanism.”

The laboratory group hopes to extend this study into tissue and animal models to see if the same actions occur.