June 11, 2019

Research led by Wayne M.D./Ph.D. student could lead to treatment for fatty liver disease

Half of individuals of Hispanic descent carry a gene variant in their DNA that causes fatty liver disease, a buildup of fat inside liver cells that makes it harder for the liver to work. Despite the prevalence, no drug therapies exist to treat the condition.

A discovery made by a student and researchers at the Wayne State University School of Medicine may change that.

Alex Yang
Alexander Yang is in his fifth year of the M.D./Ph.D. graduate program at Wayne State University.

Alexander Yang is in his fifth year of the Wayne State University School of Medicine’s M.D./Ph.D. combined degree program, and was the driving force behind “Dynamic Interactions of ABHD5 with PNPLA3 regulate triacylglycerol metabolism in brown adipocytes,” published last month in the journal Nature Metabolism.

The article investigates the mechanism by which the I148M variant, a common variant in the Patatin-like phospholipase domain-containing protein 3 enzyme, or PNPLA3, causes fatty liver disease, also known as hepatic steatosis. Despite its prevalence, the mechanism by which the I148M variant – a single nucleotide polymorphism genotype – actually causes the disease remains controversial.

“Our article suggests that the I148M variant mechanism of fatty liver disease is through the interaction between PNPLA3 and ABHD5, the master regulator of lipolysis. This interaction is affected by synthetic ABHD5 ligands, which suggests that ABHD5 ligands could potentially be developed as a therapy for fatty liver patients with the variant,” Yang said.

Understanding the mechanism by which the I148M variant causes fatty liver disease could lead to new drug therapies, he added.

Yang is mentored by James Granneman, Ph.D., a professor in the Center for Molecular Medicine and Genetics. The research team included Emilio Mottillo, Ph.D., who earned his doctorate at Wayne State and is now at Henry Ford.

Yang’s project was partially funded by a Ruth L. Kirschstein National Research Service Award (F30 grant) from the National Institute of Diabetes and Digestive and Kidney Diseases, which also funds his stipend and educational expenses.