Targeting fatty acids may become a treatment strategy for arthritis

Enzymes linked to diabetes and obesity seem to play key roles in arthritis and leukaemia, potentially opening up new avenues for treating these diverse diseases, according to new research published in Cell Metabolism.
Working with genetically engineered mice, experts found that the same enzymes involved in turning carbohydrates into the building blocks of fats also influence the health of white blood cells called neutrophils. Neutrophils are the most common type of white blood cell and a hallmark of inflammation, a key component of rheumatoid arthritis. (Abnormally high levels of neutrophils also are common in patients with leukaemia.)
“The link between these enzymes and neutrophils was a big surprise,” says Dr Irfan J Lodhi, who is involved in the work.
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.
The discovery could lead to the targeting of ether lipids as a way to reduce the number of neutrophils in inflammatory diseases and leukaemia. The researchers believe limiting, rather than eliminating, ether lipids may be the best approach because neutrophils are needed to fight infections.
“This may be a pathway to limit inflammation,” explains Dr Clay F Semenkovich, who led the work. “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 leukaemia and inflammatory diseases such as arthritis.”
The enzymes specifically target neutrophils without affecting other immune cells, so the ether lipids are a precise target.
The group found that inactivating the enzymes only killed older neutrophils. This means that strategies to limit the production of ether lipids might lower neutrophil levels temporarily so that when treatment stops, a patient’s neutrophil count gradually would rise, allowing the immune system to return to normal.

Image credit: Hans Splinter

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