Opposite Effects of Metformin against Non-Alcoholic Fatty Liver Disease, Depend on Steatosis Grade

Currently, as there are no standardized treatment regimen for non-alcoholic fatty liver disease (NAFLD) and the assumption of insulin resistance involved in NAFLD, so, the effectiveness of medicines of type 2 diabetes mellitus including metformin is expected. Despite of the precise mechanism remaining controversial, metformin has been reported to activate AMP-activated protein kinase (AMPK) which is a master regulator of energy homeostasis, and is activated in response to an energy shortage imposed by physical activity and caloric restriction. In our study to investigate the metformin effectiveness on NAFLD, the opposite effects were found. Specifically, there has been shown that metformin well ameliorated mild steatosis, but aggravated high grade of steatosis to hepatitis and fibrosis (NASH), which were seemed closely related to liver mitochondrial dysfunction. The molecular mechanism of metformin to activate AMPK was demonstrated by the consequence to inhibit the complex I of mitochondrial respiratory chain, which is interpreted as a poison to mitochondrial energy metabolism, especially, when a certain degree damage exists in mitochondria. So, we here put the results and state opinion for expansion of metformin indications safely and efficiently.