Reducing fatty acid production may help treat arthritis, leukemia

A new study by researchers from the Washington University School of Medicine in St. Louis claims fatty acids associated with obesity and diabetes may also contribute to the development of arthritis and leukemia, paving the way for new treatments for these diseases.

The top picture shows normal ether lipid production in mice, alongside an abundance of neutrophils. The bottom picture shows reduced neutrophils in mice with impaired ether lipid production.
Image credit: Washington University School of Medicine

The researchers at the Division of Endocrinology, Metabolism and Lipid Research, reveal that enzymes that play a role in converting carbohydrates to a certain type of fatty acid - called an ether lipid - play a role in the health of neutrophils.

Neutrophils are a type of white blood cell that helps ward off infections in the body, especially those caused by bacteria or fungi.

However, an abnormally high number of neutrophils present in the blood - referred to as neutrophilia - can be a sign of acute inflammation and is associated with rheumatoid arthritis. Neutrophilia is also common among individuals with leukemia.

Without ether lipids, neutrophils die

For their study, published in the journal Cell Metabolism, the research team analyzed genetically engineered mice. These mice were unable to create the enzymes that produce ether lipids.

They found that without ether lipids, the mice rapidly lost weight and their white blood cell count became very low. In particular, the mice displayed extremely low levels of neutrophils; they found that lack of ether lipids appeared to kill neutrophils.

Around 52.5 million adults in the US have some form of arthritis, and it is estimated that there were around 52,380 new cases of leukemia diagnosed last year, with 24,090 deaths from the disease.

But the researchers believe their findings could open the door to new treatments for both of these conditions:

"This may be a pathway to limit inflammation. If we could reduce the activity of these enzymes without eliminating them entirely, it could lower the levels of ether lipids and potentially help patients with leukemia and inflammatory diseases, such as arthritis."

Defective enzymes only killed mature neutrophils

In addition, the researchers found that the enzymes that were unable to produce ether lipids solely targeted neutrophils and avoided killing other white blood cells. What is more, the enzymes only killed mature neutrophils, avoiding their precursors.

According to the team, this means that reducing production of ether lipids would only lower neutrophil levels temporarily, meaning a patient's neutrophil count would increase - normalizing the immune system - once treatment ceases.

The researchers had never thought about treating rheumatoid arthritis or leukemia by targeting enzymes that produce fatty acids, but this work supports that line of thinking.

References:

1.  Peroxisomal lipid synthesis regulates inflammation by sustaining neutrophil membrane phospholipid composition and viability, Clay F. Semenkovich, et al., Cell Metabolism, doi: http://dx.doi.org/10.1016/j.cmet.2014.12.002, published 6 January 2015, abstract.
2.  Washington University School of Medicine news release, accessed 7 January 2015 via EurekAlert.
3.  Additional source: Centers for Disease Control and Prevention, arthritis-related statistics, accessed 7 January 2015.
4.  Additional source: American Cancer Society, leukemia statistics, accessed 7 January 2015.