Obesity-Induced Fatty Liver Disease Reversed in Mouse Models

A recent study looks at how obesity-induced fatty liver disease can actually be reversed in mice with the help of the drug valproic.

This disease can cause liver failure and is often an obesity related issue, according to background information from the study.

Researchers examined the cytochrome P450 family of enzymes and how they process valporic acid. The study showed that it can activate the protein AMPK that is already known to be a good target for such health issues as type 2 diabetes and obesity.

The study notes the following regarding the drug, courtesy of a press release: "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 said, via the release. "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."

As the valproic acid is extremely processed by cytochrome P450 enzymes, the researchers added a cytochrome P450 inhibitor to both mouse and human liver cells. They found that AMPK was longer activated. To test this further, they added four chemically modified versions of the drug to cells. They also found that the derivatives were able to activate the AMPK without valproic acid.

With the help of the drug, blood sugar levels in mice were lowered and they were able to decrease in size and accumulation of fat stored in their livers.

"The improvements seen in the health of these obese mice were very encouraging," Bumpus concluded. "We hope that we will find similar results in obese people who take valproic acid."

More information regarding the study can be found via the journal Molecular Pharmacology.