Georgia State Researchers Explore Biological Processes That Reduce Fat

ATLANTA—Georgia State biologists have made new discoveries about the processes by which humans and other mammals burn energy and fat, which could lead to new therapies for obesity and Type 2 diabetes.

The research focuses on how white fat (or white adipose tissue) which stores excess energy, is converted into brown fat, which dissipates energy through the production of heat. This process, called “beigeing” is initiated in humans and other mammals in response to cold conditions as the body attempts to maintain proper temperature. After an initial shivering response to cold, a nonshivering phase occurs, in which brown adipose tissue (BAT), or brown fat is activated for heat production through a process called thermogenesis.

The research presents an opportunity to harness the temperature-regulating (or thermogenic) potential of these tissues in the fight against obesity and Type 2 diabetes, said biology professor Hang Shi.

“Obesity is all about the energy imbalance caused by energy/food intake that exceeds energy expenditure," he said. "By activating the sympathetic nerves that control white adipose tissue, we can increase the expenditure of energy in the body.”

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. Mitochondria are the parts of cells that turn sugars, fats and proteins into forms of chemical energy.

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. Epigenetics is the study of changes in organisms that result from how the environment affects the ways genes express an individual’s genetic code rather than alteration of the genetic code itself.

The researchers hope their insights can identify new potential ways to use brown fat in the prevention and treatment of obesity.

In the current study, Shi and his collaborators injected laboratory mice with a chemical neurotoxin to allow them to study how sympathetic nerves regulate beige cell formation in increasingly cold temperatures. The researchers were surprised to observe that the mice were able to compensate for a lack of functional brown fat by converting white fat to beigeing adipose cells, thereby maintaining a normal body temperature.

“Our previous work demonstrated the importance of brown fat function in energy metabolism,” Shi said. “But the current study builds on that and shows that a loss of brown fat function is not fatal in cold temperatures. We see that this loss of brown fat can be compensated by the beigeing of white fat cells through the sympathetic nerves.

Shi’s co-authors for the study include Georgia State biology professor Bingzhong Xue and post-doctoral research associates Qiang Cao, Jia Jing and Xin Cui.

The article, “Sympathetic nerve innervation is required for beigeing in white fat” was published in the journal Physiological Reports.

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