New Insights into Fat Metabolism: Researchers Discover Potential Obesity Treatment
In a groundbreaking development, researchers from the Institute for Basic Science (IBS) have made significant progress in understanding the regulation of fat metabolism. Led by Director C. Justin LEE, the team focused on a specific type of brain cells called astrocytes and successfully used a new drug called KDS2010 to achieve weight loss in mice without dietary restrictions. This discovery brings hope to the one billion individuals worldwide affected by obesity.
The hypothalamus in the brain plays a crucial role in maintaining the balance between food intake and energy expenditure. While the connection between neurons in the lateral hypothalamus and fat tissue had been previously known, their exact role in fat metabolism regulation remained a mystery. The researchers identified a cluster of neurons in the hypothalamus that express the receptor for the inhibitory neurotransmitter GABA, which they termed the GABRA5 cluster.
Using a diet-induced obese mouse model, the researchers observed a significant decrease in the activity of the GABRA5 neurons. They then experimented with inhibiting the activity of these neurons, which led to a reduction in energy consumption and weight gain in the mice. Conversely, activating the GABRA5 neurons resulted in successful weight reduction. This suggests that these neurons may act as a switch for weight regulation.
However, the researchers made an unexpected discovery when they found that astrocytes in the lateral hypothalamus regulate the activity of the GABRA5 neurons. Reactive astrocytes were found to overexpress the MAO-B enzyme, which produces a large amount of inhibitory GABA that suppresses the GABRA5 neurons. By suppressing the expression of the MAO-B gene in reactive astrocytes, the researchers were able to decrease GABA secretion and reverse the inhibition of the GABRA5 neurons.
To test the effectiveness of this approach, the researchers used the MAO-B inhibitor KDS2010, which is currently undergoing Phase 1 clinical trials. The drug yielded remarkable results in an obese mouse model, significantly reducing fat accumulation and weight without impacting food intake.
Postdoctoral researcher SA Moonsun highlighted the importance of targeting non-neuronal astrocytes in obesity treatment, stating that previous treatments focused mainly on neuronal mechanisms related to appetite regulation. Center Director C. Justin LEE emphasized the significance of their findings as obesity is considered an emerging infectious disease by the World Health Organization.
The research results were recently published in the prestigious academic journal Nature Metabolism, further solidifying the significance of this breakthrough. With the potential of KDS2010 as a next-generation obesity treatment, there is renewed hope for individuals struggling with obesity worldwide.
Source: Institute for Basic Science