School of Medicine scientists have identified a substance in the liver that helps process fat and glucose. That substance is a component of the common food additive lecithin, and researchers speculate it may one day be possible to use lecithin products to control blood lipids and reduce risk for diabetes, hypertension or cardiovascular disease using treatments delivered in food rather than medication.
Semenkovich
“Doctors use drugs called fibrates to treat problems with cholesterol and triglycerides,” said the study’s co-first author Irfan J. Lodhi, Ph.D., a postdoctoral fellow in endocrinology and metabolism. “By identifying this substance that occurs naturally in the body — and also happens to be used as a food additive — it may be possible to improve the treatment of lipid disorders and minimize drug side effects by adding particular varieties of lecithin to food.”
Lecithin is found at high concentrations in egg whites and also is in soybeans, grains, fish, legumes, yeast and peanuts. Most commercially used lecithin comes from soybeans. Lecithin can alter food taste and texture and also can be mixed with water to disperse fats, making it a common additive in margarine, mayonnaise, chocolate and baked goods. Lecithin is a mixture of fatty compounds called phosphatidylcholines. Various types of phosphatidylcholines house different kinds of fatty molecules linked to a common core.
The study demonstrates that in the liver, a specific type of lecithin binds with a protein called PPAR-alpha, allowing PPAR-alpha to regulate fat metabolism. Scientists long have known that PPAR-alpha is involved in lipid and glucose metabolism. When doctors prescribe fibrate drugs to lower triglycerides and elevate good cholesterol in the blood, those drugs work by activating PPAR-alpha.
Although fibrates activate the protein, no one previously had identified any naturally occurring substance that could perform that task. In the Aug. 7 issue of Cell, the research team described how it found the link between lecithin and PPAR-alpha.
They first created a strain of mice that could not make fatty acid synthase in the liver. When humans or animals eat, they take in sugars. Fatty acid synthase converts those sugars to fatty acids in the liver, where they play important roles in energy metabolism.
“To our surprise, animals missing fatty acid synthase in the liver were just like animals that couldn’t make PPAR-alpha,” said senior investigator Clay F. Semenkovich, M.D., the Herbert S. Gasser Professor and chief of the Division of Endocrinology, Metabolism and Lipid Research. “They had lower fasting insulin levels, and they were prone to develop fatty liver disease. When we gave the animals fibrate drugs that activated PPAR-alpha, the mice returned to normal, leading us to suspect that fatty acid synthase also was involved in the activation of PPAR-alpha.
“Although we knew that fibrate drugs would regulate PPAR-alpha, we also knew that our ability to regulate the metabolism of fats and sugars was in place long before humans started making drugs,” Semenkovich said. “But until now, no one had identified how it worked.”
Semenkovich, Lodhi, John Turk, M.D., Ph.D., professor of medicine and of pathology, and the team used mass spectrometry and gene expression studies to isolate the phosphatidylcholine, or lecithin compound, that activated PPAR-alpha in the liver.
It’s fortunate, Semenkovich said, that an extremely common compound like lecithin binds to a key drug target like PPAR-alpha.
“That information could be used to make better drugs or even to develop what people sometimes refer to as nutriceuticals — nutrients that have pharmaceutical-like properties,” Semenkovich said.