Credit: The Jackson Laboratory
Johns Hopkins researchers have discovered that valproic acid, a widely prescribed drug for treating epilepsy, has the additional benefits of reducing fat accumulation in the liver and lowering blood sugar levels in the blood of obese mice. A summary of their research appears in this month’s issue of the journal Molecular Pharmacology.
Fatty liver disease can lead to liver failure and is often caused by obesity and a high-fat diet. Obesity is also associated with the development of type 2 diabetes, which sabotages the body’s process for controlling blood sugar levels. A rapidly rising problem in the developed world, obesity currently affects over 90 million Americans.
Studying the ways in which the cytochrome P450 family of enzymes processes valproic acid, the Johns Hopkins biochemists found that it can activate the protein AMPK, which was already known to be a good drug target for treating metabolic disorders like type 2 diabetes and obesity.
The Bumpus laboratory studies how drugs are processed in cells by enzymes of the cytochrome P450 family. Humans have 57 of these enzymes, and several of them work on the drug valproic acid. In the course of their research, Namandjé Bumpus, Ph.D., assistant professor of pharmacology, and postdoctoral fellow Lindsay Avery, Ph.D., found that valproic acid could activate AMPK in mouse and human liver cells in a dose-dependent way.
“It was exciting to find that valproic acid can activate AMPK,” Bumpus says. “What’s even better is that its byproducts can activate AMPK at much lower doses. That’s a desirable quality if you want to eventually use it to treat people.”