Researcher at OU Health Harold Hamm Diabetes Center Earns Grant to Study Development of Advanced Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications.

Many people today live with NAFLD, an excess of fat stored in the liver that often occurs with obesity and Type 2 diabetes. Some people have the condition for years with little to no harmful effects, but a small percentage slowly develop NASH, or non-alcoholic steatohepatitis, an advanced form of fatty liver disease that can lead to cirrhosis and liver cancer.

Why some people develop NASH and others don’t is not well understood. Tiangang Li, Ph.D., a researcher at OU Health Harold Hamm Diabetes Center, recently received a $1.6 million grant from the National Institutes of Health to better understand how NASH begins and whether any part of its progression could be targeted for drug development.

“Researchers have begun to realize that people with fatty liver disease may develop NASH for different reasons, or a combination of different reasons,” Li said. “It is important to better understand how the disease develops because we don’t currently have a drug to treat NASH.”

Traditionally, research into fatty liver disease has focused on the accumulation of fat itself. When fat accumulates in the liver, it is metabolized and converted into other metabolites that can be toxic in the cells. However, chronic liver fat accumulation is not the only factor driving the development of NASH; otherwise, most people with liver fat accumulation would develop NASH. Li’s laboratory is instead focusing on amino acid metabolism.

Amino acids are the building blocks of proteins, but they are also metabolized for functions other than protein production. Recent research has shown that, in patients with advanced NASH, the metabolism of a specific type of amino acids, sulfur amino acids, is altered. For this study, Li is looking closely at methionine and cysteine, two types of sulfur amino acids. Methionine is converted to cysteine, and one of the functions of cysteine is to produce Coenzyme A (CoA), which the liver needs to burn fat and prevent fat accumulation. Previous studies have demonstrated that a deficiency in CoA can limit the liver’s ability to burn fat and, at the same time, cause oxidative stress and mitochondrial dysfunction, which lead to cellular injury.

“We think one of the drivers of NASH development may be the reduced ability of the liver to produce CoA,” Li said. “This focus on sulfur amino acids is an exciting and emerging field. Fatty liver disease is complex and many factors play a role in it. Study of the role of sulphur amino acids and their metabolism in NASH progression may lead to better understanding of this complex condition.”

Research reported in this news release is supported by the National Institute of Diabetes and Digestive and Kidney Diseases, a component of the National Institutes of Health, under the award number 1R01DK131064-01.