Georgia State Biologist Awarded Grant to Study How Nerves Regulate Fat, Metabolism

ATLANTA-Professor Hang Shi, associate chair of Georgia State University's Department of Biology, has been awarded a five-year grant from the National Institutes of Health (NIH) worth $3.46 million to study how the body's nerves regulate fat and metabolism - research that could eventually contribute to new treatments for obesity.

The grant, funded through the National Institute of Diabetes and Digestive and Kidney Diseases, will support research into nerves that connect to fat tissue throughout the body. These nerves send signals that help specialized fat cells burn energy and produce heat. Shi's lab wants to understand the factors that control how those nerves evolve over time.

"We are asking how the nerves connected to fat tissue help the body burn energy, and whether we can improve that process," Shi said.

Not all fat works the same way, Shi explained. White fat, the kind most people think of, mainly stores energy. But the body also has brown and beige fat, which burns fuel to produce heat instead of storing it. Nerves trigger that heat-producing process, and Shi's team wants to know how the body adapts these nerve connections in response to cold and diet.

His lab will focus on an enzyme called DNMT3A, which helps regulate gene activity inside nerve cells without changing the underlying DNA sequence. Shi wants to know whether DNMT3A affects how these nerves grow, how much heat brown and beige fat produce, and how susceptible mice are to obesity.

Many widely used obesity medications, including GLP-1-based drugs, primarily work by reducing appetite and food intake. Shi's research points toward a different approach: Increasing the body's energy use through brown and beige fat. If the mechanisms also operate in humans, they could eventually complement existing obesity treatments.

The current project, however, is limited to cells and mice. Further research would be needed to establish whether the findings are relevant to humans and to evaluate safety and effectiveness before they could lead to a treatment or diagnostic test.

"What remains unclear is how the nerves themselves grow and adapt within fat tissue, and whether changing their molecular controls can produce metabolic benefits," Shi said. "Our project examines those questions in experimental models."

The work builds on Shi's decades-long research studying how the regulation of gene activity influences metabolic pathways involved in obesity, diabetes, fatty liver disease and atherosclerosis. Earlier research from his team found that removing DNMT3A from sympathetic nerve cells increased nerve growth and energy expenditure - a finding that helped shape the questions behind the new project.

Three doctoral students in Shi's lab will contribute to the research by designing experiments, studying nerve growth and fat function, and analyzing molecular and physiological data.

"The project will give them experience connecting a question about gene regulation to its consequences for the whole organism," Shi said. "I see their development into independent scientists as an important part of what this grant can accomplish."

Shi said success five years from now would mean showing how changes in gene activity control nerve growth in fat tissue, and whether altering that activity can meaningfully affect how much energy the body burns and how susceptible it is to obesity.

"I hope our findings give the field a stronger basis for developing ways to improve metabolic health by regulating the communication between nerves and fat," he said.

Shi's co-principal investigator on the grant is Distinguished University Professor of Biology Bingzhong Xue. The project runs through June 2031.