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Epilepsy drug reverses fatty liver disease in obese mice

A commonly used epilepsy drug may be able to stop fatty liver disease and prevent Type 2 diabetes in obese people, according to a new study by Johns Hopkins researchers.

Scientists found that valproic acid, an anticonvulsant and mood-stabilizing drug prescribed to epilepsy patients, reduced fat accumulation in the liver and lowered blood sugar levels in obese mice. Obesity and a high-fat diet is often associated with the development of Type 2 diabetes and can also cause fatty liver disease, and in some cases, liver failure.

Researchers added a cytochrome P450 inhibitor to mouse and human liver cells and found that the protein AMPK, a validated target for treating metabolic disorders like Type 2 diabetes and obesity, was no longer activated. Valproic acid is known to be extensively processed by the family of cytochrome P450 enzymes.

This suggested that the byproducts of valproic acid, as opposed to valproic acid itself, were activating AMPK. To test this, the scientists added four chemically modified versions of the drug to the cells and found that the derivatives not only activated AMPK without valproic acid but they also achieved higher activation of AMPK at a much smaller concentration. The findings appear in the journal Molecular Pharmacology.