New drug to fight liver disease

A drug currently used to treat diabetes shows potential for combating liver disease in non-alcoholics, according to researchers at Kanazawa University.

Toshinari Takamura and co-workers tested whether the drug metformin could work against nonalcoholic steatohepatitis (NASH), which causes inflammation, fat build-up and fibrosis in the liver, and can lead to cirrhosis – permanent loss of liver tissue. Steatohepatitis is common in alcoholic, diabetic and obese patients, but effective treatments for non-alcoholic, non-diabetic patients are limited.

Metformin is believed to restrain glucose generation in the liver by activating a protein kinase called AMPK, which suppresses the cells involved in fibrosis, induces antioxidant enzymes and blocks the cell cycle. This group previously showed that when metformin was given to obese diabetic mice, it altered the expression of genes related to glucose and lipid metabolism in the liver.

In their latest study, the researchers fed non-diabetic mice a high-fat, low-nutrient diet for eight weeks to induce NASH symptoms. Half the mice were treated with metformin during this time, which significantly reduced the inflammation and fibrosis in their livers. What’s more, the results showed that metformin could reverse symptoms even after NASH had fully developed.

The researchers found that this reduction in symptoms was associated with reduced triglyceride content and downregulation of genes involved in fatty acid metabolism, inflammation and fibrosis. Best of all, metformin does not affect insulin resistance. Takamura and co-workers conclude that metformin shows great potential for human use, and suggest that clinical trials should begin as soon as possible.

Publication and Affiliation
Yuki Kita1, Toshinari Takamura1,*, Hirofumi Misu1, Tsuguhito Ota1, Seiichiro Kurita1, Yumie Takeshita1, Masafumi Uno1, Naoto Matsuzawa-Nagata2, Ken-ichiro Kato1, Hitoshi Ando3, Akio Fujimura3, Koji Hayashi4, Toru Kimura4, Yinhua Ni1, Toshiki Otoda1, Ken-ichi Miyamoto2, Yoh Zen5, Yasuni Nakanuma5 & Shuichi Kaneko1. Metformin prevents and reverses inflammation in a non-diabetic mouse model of non-alcoholic steatohepatitis. PLOS One 7(9), e43056 (2012) Link

1. Department of Disease Control and Homeostasis, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan
2. Department of Hospital Pharmacy, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan
3. Division of Clinical Pharmacology, Department of Pharmacology, School of Medicine, Jichi Medical University, Tochigi, Japan
4. Genomic Science Laboratories, Dainippon Sumitomo Pharma Co. Ltd., Osaka, Japan
5. Department of Human Pathology, Kanazawa University Graduate School of Medical Science, Ishikawa, Japan

*corresponding author, e-mail address: ttakamura@m-kanazawa.jp

ID: 201212B005