Targeting fatty acids may be treatment strategy for arthritis, leukemia

The bone marrow of mice with normal ether lipid production (top) contains more white blood cells than are found in the bone marrow of mice with ether lipid deficiency (bottom).
Credit: Washington University School of Medicine

Enzymes linked to diabetes and obesity appear to play key roles in arthritis and leukemia, potentially opening up new avenues for treating these diverse diseases, according to new research at Washington University School of Medicine in St. Louis.

Working with genetically engineered mice, the researchers discovered that the same enzymes involved in turning carbohydrates into the building blocks of fats also influence the health of specialized white blood cells called neutrophils. Neutrophils are the most abundant type of white blood cell and a hallmark of inflammation, which is a key component of rheumatoid arthritis. Abnormally high levels of neutrophils also are common in patients with leukemia.

The study is published Jan. 6 in the journal Cell Metabolism.

"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.

"So ether lipids appear to be a very precise target," he said.

Working with Daniel Link, MD, the Alan A. and Edith L. Wolff Distinguished Professor of Medicine, the researchers 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 gradually would rise, allowing the immune system to return to normal.

Source: Washington University in St. Louis

Moderate consumption of sugary drinks has little impact on adolescents' metabolic health

Sugar-sweetened beverages, such as soft drinks, are the largest source of added sugar in the diets of adolescents in the United States. Credit: Image courtesy of University of Missouri-Columbia

Sugar-sweetened beverages are the largest source of added sugar in the diets of adolescents in the United States, and young adults ages 15-20 consume more of these drinks than any other age group, according to the Centers for Disease Control and Prevention. Adolescent obesity rates, which have quadrupled over the past thirty years, led to widespread scrutiny of added dietary sugars, especially those found in carbonated beverages. Now, MU researchers have found that short-term, moderate consumption of high-fructose and high-glucose beverages has little impact on the metabolic health of weight-stable, physically active adolescents.

"These beverages may not be as unhealthy for adolescents as previously thought, provided that kids stay active," said Jill Kanaley, professor and associate chair in the MU Department of Nutrition and Exercise Physiology. "That physical activity component is really critical in protecting against some of the negative effects of drinking large amounts of sugar-sweetened drinks demonstrated in previous studies."

Kanaley's study measured several aspects of metabolic health, including insulin sensitivity and cholesterol levels, after participants had consumed moderate amounts of either high-glucose or high-fructose beverages every day for two weeks. The high-glucose drink contained 50 grams of glucose and 15 grams of fructose; the high-fructose drink contained 50 grams of fructose and 15 grams of glucose. In comparison, two 12-ounce cans of white soda contain about 50 grams of fructose, although the amount of sugar found in soft drinks varies by brand and type. The researchers used armbands with electronic sensors to monitor physical activity of the participants, all of whom were healthy male and female adolescents ages 15-20.

Although some research has shown that consuming sugary drinks can have detrimental metabolic effects, Kanaley said that the results of these studies have been inconsistent. Previous research often has excluded adolescents and did not measure participants' levels of physical activity. In one of her previous studies, which recently was published in Medicine in Science and Sports, Kanaley found that increased physical activity diminished negative effects associated with high-fructose diets.

"Many parents of adolescents worry about their children's consumption of sweetened beverages," Kanaley said. "I certainly would recommend that they work to reduce their children's intake of sugary drinks, but it also is important for kids to remain active, especially if they are drinking a lot of sugary beverages. In our study, the female adolescents averaged around 8,000 steps per day, and the males averaged about 10,000 steps per day. 

These children weren't athletes, but they had active lifestyles."

Kanaley's article was published in the American Journal of Clinical Nutrition.

Source: University of Missouri-Columbia