DAEJEON, South Korea — For many individuals struggling with obesity and weight loss, nothing is more difficult than limiting themselves to just one true serving of their favorite foods. Now, people could soon be eating all they want without putting on weight following a breakthrough discovery of an obesity switch in the brain. Scientists have found what controls a cluster of neurons in the brain that regulates fat expenditure.
The study by researchers at the Institute for Basic Science in Korea could lead to the end of obesity for a billion people worldwide. Led by Director C. Justin Lee from the institute’s Center for Cognition and Sociality, the team also reported successful animal trials of a new drug, KDS2010, which helped mice lose weight without cutting down on their food intake.
“Given that obesity has been designated by the World Health Organization (WHO) as the ’21st-century emerging infectious disease,’ we look to KDS2010 as a potential next-generation obesity treatment that can effectively combat obesity without suppressing appetite,” Lee says in a statement.
The research zeroes in on the brain’s hypothalamus, which has long been known to play a role in balancing food intake and energy spent. However, the exact function of certain neurons—nerve cells—in this part of the brain has been a subject of mystery. The scientists identified a specific group of neurons that contain a receptor for GABA (Gamma-Aminobutyric Acid), a molecule that acts as a messenger in the brain. This group of neurons, named the GABRA5 cluster, seems to act like a switch in controlling weight.
Interestingly, it was not just the neurons that the researchers focused on. They also turned their attention to astrocytes, star-shaped non-neuronal cells in the brain. The team found that these astrocytes can affect the activity of the GABRA5 neurons by producing a large amount of GABA. In simpler terms, astrocytes can put the brakes on the neurons that could otherwise help with weight loss.
These astrocytes overproduce an enzyme called MAO-B (Monoamine Oxidase B), which plays a vital role in how neurotransmitters—chemicals that send signals in the brain—are broken down. By controlling the production of this enzyme, the researchers could essentially “switch on” the weight-loss activity of the targeted neurons in mice, even when the mice were on a high-calorie diet.
“Previous obesity treatments targeting the hypothalamus mainly focused on neuronal mechanisms related to appetite regulation,” says postdoctoral researcher Moonsun Sa. “To overcome this, we focused on the non-neuronal ‘astrocytes’ and identified that reactive astrocytes are the cause of obesity.”
Researchers are now hoping to realize the potential of their findings for human applications with the drug KDS2010, which is currently in Phase 1 clinical trials. With the drug dramatically reducing fat and weight in the mice regardless of the food they ate, the medication could be useful for countless individuals struggling with obesity, addressing a global health issue head-on.
The results of this research were published in the journal Nature Metabolism.
South West News Service writer Jim Leffman contributed to this report.