Navigation Links
Obesity-induced fatty liver disease reversed in mice

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, Namandj 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."

Knowing that valproic acid is extensively processed by cytochrome P450 enzymes, the research team added a cytochrome P450 inhibitor to mouse and human liver cells and found that AMPK was no longer activated. This suggested that the byproducts of valproic acid, as opposed to valproic acid itself, were the molecules activating AMPK. To test this theory, they added four chemically modified versions of the drug to the cells and found that the derivatives were able to activate AMPK without valproic acid. In fact, they achieved higher activation of AMPK at one-fortieth the concentration.

To assess the uptake and breakdown of valproic acid in living organisms, they gave the drug to obese mice with high blood sugar levels, fatty livers and rapid weight gain. Treated mice showed decreased blood sugar levels, decreases in the size and the fat accumulation of their livers, and a stabilization of weight rather than the continued weight gain experienced by untreated mice.

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


Contact: Catherine Kolf
Johns Hopkins Medicine

Related medicine news :

1. Fatty acid found in fish prevents age-related vision loss: U of A medical research
2. Pictures of Fatty, Sugary Foods May Spur Cravings
3. Girls with eating disorders regain healthy fatty acid levels when their weight normalizes
4. Analysis of conflicting fish oil studies finds that omega-3 fatty acids still matter
5. Scripps Florida scientists develop new compound that reverses fatty liver disease
6. Limiting polyunsaturated fatty acid levels in pregnancy may influence body fat of children
7. Fatty Liver Treatment
8. How “Fatty Liver Diet Guide” Helps People Treat Fatty Liver Quickly –
9. Omega-3 fatty acids more effective at inhibiting growth of triple-negative breast cancer
10. Scarring May Raise Death Risk From Fatty Liver Disease
11. Gene variant ID could lead to better fatty liver disease diagnosis
Post Your Comments:
Related Image:
Obesity-induced fatty liver disease reversed in mice
(Date:11/27/2015)... ... , ... ProSidebar: Fashion is a set of 30 kinetic edge ... video editors can easily add an informative sidebar to any FCPX production. Create ... featuring self-animating drop zones, lines, bars, and text with the ease of FCPX's drag ...
(Date:11/27/2015)... ... ... A simply groundbreaking television series, "Voices in America", which is hosted by Hollywood ... issues that are presently affecting Americans. Dedicated to providing the world with a wide ... subjects consumers focus on, one episode at a time. , In the latest ...
(Date:11/27/2015)... IL (PRWEB) , ... November 27, 2015 , ... ... of the largest, most successful and prominent nonprofit healthcare organizations in the country. ... governance involvement with various organizations, and helped advance the healthcare industry as a ...
(Date:11/26/2015)... ... 26, 2015 , ... Patients at Serenity Point Recovery, a ... on Thanksgiving Day to share the things that they are most grateful for ... YouTube channel, patients displayed what they wrote on index cards, describing the things ...
(Date:11/26/2015)... ... ... The Catalent Applied Drug Delivery Institute today announced a ... selection in early phase drug development. The first of these is to be ... UK’s emerging life sciences companies, corporate partners, and investors, at Milton Park, Oxford, ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... 26, 2015 Un nuevo enfoque ... para el cáncer avanzado.   --> ... fotodinámica de Bremachlorin para el cáncer avanzado.   ... inmunoterapia con la terapia fotodinámica de Bremachlorin para el ... . --> Clinical Cancer Research . ...
(Date:11/26/2015)... -- Research and Markets ( ) has announced the ... to 2019 - Rise in Cardiac Disorders and Growing Awareness ... their offering. Boston scientific ... scientific and others. --> The market is ... Boston scientific and others. ...
(Date:11/26/2015)... November 26, 2015 ... the "2016 Future Horizons and Growth ... Testing Market: Supplier Shares, Country Segment Forecasts, ... their offering. --> ) ... "2016 Future Horizons and Growth Strategies in ...
Breaking Medicine Technology: