Corporate Banner
Satellite Banner
Metabolomics & Lipidomics
Scientific Community
Become a Member | Sign in
Home>News>This Article

Fatty Liver Disease Reversed in Mice

Published: Thursday, January 30, 2014
Last Updated: Thursday, January 30, 2014
Bookmark and Share
Epilepsy drug also shown to decrease obesity-related blood sugar levels.

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. 

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.”

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.”

A summary of the research appears in this month’s issue of the journal Molecular Pharmacology.

This work was supported by a grant from the National Institute of General Medical Sciences (R01GM103853).

Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,500+ scientific posters on ePosters
  • More than 5,200+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Scientific News
Cell Metabolism Linked to Spread of Cancer
Scientists discover macrophage metabolism can be attuned to prevent the spread of cancer.
Integrated Omics Analysis
Studying multi-omics promises to give a more holistic picture of the organism and its place in its ecosystem, however despite the complexities involved those within the field are optimistic.
Fatty Liver Disease Linked to Type 2 Diabetes
Recent study identifies factors causing insulin to misbehave in non-alcoholic fatty liver disease.
New Pathway for COPD Biomarker Development
A study from Philip Morris International has highlighted multi-lipid profiling as a potential new pathway for COPD biomarker development.
Lab-on-a-Chip Detects Effects of Poison
A fast and efficient mixer has been developed for testing the effect of toxic substances faster by using a new lab-on-a-chip.
Clinical Trial Finds Medicine Program Alters Blood Serum
Meditation, yoga and vegetarian diet linked to decline in plasma metabolites associated with inflammation and cardiovascular disease risk.
3D-Printing in Science: Conference Co-Staged with LABVOLUTION
LABVOLUTION 2017 will have an added highlight of a simultaneous conference, "3D-Printing in Science".
Targeting Cardiovascular Disease Risk Factors May be Important Across a Lifetime
The study suggests efforts to prevent risk factors should extend to those older than 65.
Beige Fat Formation Linked to Anti-diabetic Effect
Researchers at UTSW have found that the protein connexin 43 forms cell-to-cell communication channels on the surface of emerging beige fat cells that amplify the signals from those few nerve fibers.
Adipose Tissue Secretes Factors That Activate Metabolism
Study finds brown adipose tissue secretes signalling factors that activates metabolism of fat and carbohydrates.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,200+ scientific videos