Georgia State University has received two four-year grants totaling almost $3 million from the National Institutes of Health’s National Institute of Diabetes and Digestive and Kidney Diseases to research the epigenetic mechanisms that may fuel obesity.

Hang Shi, associate professor of biology in the College of Arts and Sciences, is the lead investigator on both projects.

Epigenetics is the study of any process that alters gene expression—or the way that genes “behave”—yet does not change the underlying DNA sequence. How the body regulates gene expression is hereditary but it can also be affected by a person’s environment. For this reason, obesity experts see epigenetics as a link between environmental risk factors (such as diet and lifestyle) and genetic risk factors for the disease.

Shi’s lab is exploring the epigenetic pathways that may mediate the development of obesity. A $1.5 million grant will fund a study focused on brown fat, a mitochondria-packed tissue that burns energy rather than storing it, as white fat does. While many past studies have examined the genetic factors that regulate the function of brown fat in the body, Shi and his team are looking at the role epigenetic mechanisms play in the process. The researchers hope their insights can identify new potential ways to use brown fat in the prevention and treatment of obesity.

A $1.3 million grant will support research on epigenetic mechanisms that regulate fat accumulation in the liver. Nonalcoholic fatty liver disease, in which too much fat is stored in liver cells, is the most common form of liver disease in the U.S., affecting up to 100 million people. Obesity is one of the major risk factors for the disease, which can sometimes lead to cirrhosis, liver cancer and end-stage liver failure. Shi hopes the study results will help guide the development of new therapeutic targets to prevent the buildup of fat in the liver and treat non-alcoholic fatty liver disease in obese patients.