Targeting fatty acids may be treatment strategy for arthritis, leukemia
Washington University School of Medicine
"The link between these enzymes and neutrophils was a big surprise," said first author Irfan J. Lodhi, PhD, assistant professor of medicine. "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 senior investigator Clay F. Semenkovich, MD, the Herbert S. Gasser Professor 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."
Semenkovich, also a professor of cell biology and physiology and director of the Division of Endocrinology, Metabolism and Lipid Research, said the enzymes specifically target neutrophils without affecting other immune cells.
Original publication
Lodhi IJ, Wei X, Yin L, Feng C, Adak S, Abou-Ezzi G, Hsu FF, Link DC, Semenkovich CF; "Peroxisomal lipid synthesis regulates inflammation by sustaining neutrophil membrane phospholipid composition and viability."; Cell Metabolism, 2015.
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Original publication
Lodhi IJ, Wei X, Yin L, Feng C, Adak S, Abou-Ezzi G, Hsu FF, Link DC, Semenkovich CF; "Peroxisomal lipid synthesis regulates inflammation by sustaining neutrophil membrane phospholipid composition and viability."; Cell Metabolism, 2015.
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