A brain pathway underlying the browning of fat cells may guard against obesity, a new study from the Yale School of Medicine has found.

The study, published Oct. 9 in Cell and led by professor of Comparative Medicine and Physiology Xiaoyong Yang, identified the neurons that are key players in regulating fat burning in human bodies. By deactivating these neurons in mice, energy-burning white fat to energy-burning—thermogenic—brown fat. The transformation process protected the mice from obesity, and researchers suggest it could have the same effect in people.

“This browning process is very dynamic,” said lead author and associate research scientist in comparative medicine Hai-Bin Ruan. “It can happen very quickly. ”

The neurons the researchers studied, called AgRP neurons, are responsible for regulating how much food humans consume, and how quickly they metabolize it. But Ruan and his team did not initially expect that the neurons would play a role in the conversion of white fat to brown fat, or what the researchers called “browning.” Activating those neurons deactivates white fat cells, preventing them from burning energy. But deactivating the neurons does the opposite, activating fat cells, speeding up fat metabolism and beginning the process of browning.

“If you block [these neurons], you can suppress food intake and also promote energy expenditure,” Ruan said.

Unlike adaptive thermogenesis — the process of burning energy — which relies on long-term adaptation to the environment, the browning of fat depends on short-term environmental conditions. Active AgRP neurons support energy conservation when mice undergo fasting and release the hunger-inducing hormone ghrelin. Inactive AgRP neurons allow energy expenditure through thermogenesis, allowing mice to burn fat quickly.

The AgRP neural pathway may have evolved as a sensing mechanism to maintain energy homeostasis, Ruan said. The mechanism now works against people who want to burn fat through fasting — hunger ends up suppressing thermogenesis in fat.

Deactivating the AgRP neuron function, which activates fat-burning, may help prevent obesity in the future. In particular, ion channels in the neurons can be modified to reduce neuron activity, leading to quicker metabolism of fat.

“We cannot target fat,” said author and postdoctoral associate in comparative medicine Jay Singh. “What we can target is channels.”

According to Singh, this target shows promise for people who want to control their weight. Ruan added that increasing rates of thermogenesis by converting white fat to brown fat would be the easiest way for people to prevent obesity because changing exercise and eating behaviors can be extremely difficult.

Professor at the University of Texas Southwestern Medical Center Joel Elmquist, who was not involved in the research, noted the importance of the study in understanding the role these neurons play in quickening metabolic processes.

“If we have more and more understanding, then there are more places of potential intervention,” Elmquist said.

Shingo Kajimura, professor of cell and tissue biology at the University of California San Francisco, also said that identifying the neural circuit was an important step in the research.

Nevertheless, further research on the mechanisms behind browning will be needed to understand its therapeutic implications. Ruan suggested researching how different brain areas and different hormones like insulin and leptin, both of which play a role in metabolic and hunger regulation, work together to regulate the browning process. He said he would also like to know how drugs might affect the neural pathway.

A potential inhibitory drug might specifically target the enzyme that catalyzes the AgRP neuron activity, permitting fat cells to burn more energy and protecting the consumer from obesity.

To date, Orlistat is the only anti-obesity drug approved by the FDA. Dieting and exercise remain the most common obesity treatments.