Researchers from the Institute for Basic Science (IBS) have made a breakthrough in understanding how the brain regulates fat metabolism, according to a study published in Nature Metabolism. The researchers from the Center for Cognition and Sociality (CCS) focused on star-shaped non-neuronal cells called astrocytes in the brain.
The team discovered a cluster of neurons in the hypothalamus, which is associated with the GABRA5 receptor. This receptor plays a crucial role in regulating fat metabolism. In their investigation, the researchers found that slowing the activity of these neurons in diet-induced obese mice led to weight gain, while activating them resulted in weight loss.
Further exploring the role of astrocytes, the researchers found that these cells in the lateral hypothalamus regulate the activity of the GABRA5 neurons. They discovered that reactive astrocytes overexpressed the MAO-B enzyme, which produced tonic GABA, inhibiting the GABRA5 neurons. However, when the expression of the MAO-B gene in reactive astrocytes was suppressed, the inhibition was reversed and heat production in fat tissue increased, promoting weight loss.
To test the potential of this finding for obesity treatment, the researchers administered a selective MAO-B inhibitor called KDS2010 to obese mice. The results showed significant reductions in fat accumulation and weight. KDS2010 is currently undergoing Phase 1 clinical trials.
These findings suggest that targeting reactive astrocytes and the MAO-B enzyme could be a promising approach to treating obesity without affecting appetite. This research sheds light on the complex mechanisms of fat metabolism regulation in the brain and opens up new possibilities for obesity therapies.
The implications of this study are significant, as obesity rates continue to rise globally. Developing effective treatments that target the underlying causes of obesity, such as faulty fat metabolism regulation, could have a major impact on public health. The researchers hope that their findings will inspire further research and potential clinical applications in the future.