Common epilepsy drug helps combat obesity in early studies: Discoveries
CLEVELAND, Ohio — The anticonvulsant valproic acid, sold under the brand name Depakote, helped halt weight gain and reverse the negative medical effects of obesity in mice, according to new research from Johns Hopkins University.
The study, published online Wednesday in the journal Molecular Pharmacology, may point the way toward a new treatment for millions of obese people, if further testing proves successful.
Depakote is FDA-approved for the treatment of epilepsy, manic episodes in bipolar disorder and for the prevention of migraine headaches.
In the study, obese mice that received the drug in their water stopped gaining weight, had decreased blood sugar levels, and had improvements in the health of their livers, while obese mice that did not receive the drug continued to gain weight and did not show improvements in blood sugar or liver symptoms.
“They not only had smaller livers and their livers weighed less, but they had visibly fewer fat deposits,” said Namandjé Bumpus, assistant professor of pharmacology at Johns Hopkins and head of the lab that performed the experiments. Excess fat deposits in the liver, a condition called non-alcoholic fatty liver disease, is common in obese patients and can lead to liver cancer or liver failure.
Bumpus said the Depakote appears to be activating a key regulator of metabolism within the liver cells; something called AMP-activated protein kinase, or AMPK. It is the same way that the antiadiabetic drug Metformin works in the cell, she said.
Bumpus and her lab have been studying the way drugs are broken down in the liver, and were interested to find that one of the byproducts — or metabolites — of the breakdown of Depakote actually seems to do an even better job of activating AMPK than the drug itself does.
“The great thing about this would be a potentially lower dose [drug for patients],” Bumpus said. “The metabolites were 40 times more active at activating AMPK. If you can use a lower dose that’s always great.”
The study’s findings may seem puzzling to Depakote users who have struggled with the annoying side effect of weight gain, which can affect as many as 30 to 50 percent of those who take the drug, and is commonly cited on message boards by epilepsy, migraine and bipolar patients.
Bumpus said that it’s likely the drug works differently in lean compared to obese individuals because the physiology of the two conditions is very different. They did not test the drug on normal weight mice, and were looking at outcomes other than weight gain as well.
“It’s really comparing apples to oranges,” she said.
“I think that looking in an obese population will be really interesting and necessary to do to see if this translates to people.”
The lab will also be studying the effects of giving the drug’s metabolites to mice rather than the drug itself.