Credit: Volker Brinkmann
Enzymes linked to diabetes and obesity appear to play key roles in arthritis and leukemia, according to research published in Cell Metabolism.
Working with mice, researchers discovered that the same enzymes involved in turning carbohydrates into the building blocks of fats also influence the health of neutrophils.
“The link between these enzymes and neutrophils was a big surprise,” said study author Irfan J. Lodhi, PhD, of the Washington University School of Medicine in St. Louis.
“We had never thought about treating rheumatoid arthritis or leukemia by targeting enzymes that produce fatty acids, but this work supports that line of thinking.”
In the study, mice that couldn’t make enzymes needed to produce a certain type of fat abruptly lost weight and developed extremely low white blood cell counts, with very few neutrophils. Without this fat, called an ether lipid, neutrophils died.
That discovery could lead to the targeting of ether lipids as a way to reduce the number of neutrophils in inflammatory diseases and leukemias. The researchers believe limiting, rather than eliminating, ether lipids may be the best approach because neutrophils are important infection fighters.
“This may be a pathway to limit inflammation,” said study author Clay F. Semenkovich, MD, also of the Washington University School of Medicine.
“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.”
Dr Semenkovich said the enzymes specifically target neutrophils without affecting other immune cells, “so ether lipids appear to be a very precise target.”
The researchers also learned that inactivating the enzymes didn’t harm the precursors of neutrophils; only mature neutrophils were killed.
That could mean strategies to limit the production of ether lipids might lower neutrophil levels only temporarily so that when treatment stops, a patient’s neutrophil count would gradually rise, allowing the immune system to return to normal.
