Revolutionary Discovery Reveals Astrocytes’ Key Role in Regulating Fat Metabolism and Obesity
A groundbreaking discovery has revealed that astrocytes, star-shaped cells in the brain, play a crucial role in regulating fat metabolism and obesity. Researchers have identified that these cells act on a cluster of neurons called the GABRA5 cluster, effectively acting as a “switch” for weight regulation.
This revolutionary finding has led to the development of a new drug called KDS2010, which has shown promising results in facilitating weight loss in obese mice without reducing their food intake, even when consuming a high-fat diet. If successful in human trials, this drug could be a game-changer in obesity treatment, allowing individuals to lose weight without compromising appetite or avoiding fats.
The study, led by Director C. Justin Lee from the Center for Cognition and Sociality (CCS) within the Institute for Basic Science (IBS), focused on the role of astrocytes in regulating fat metabolism. Animal experiments using the newly developed drug KDS2010 demonstrated successful weight loss in mice without dietary restrictions.
Past research has shown that the hypothalamus in the brain oversees the complex balance between food intake and energy expenditure. While the lateral hypothalamus neurons are connected to fat tissue and involved in fat metabolism, their specific role in regulation has remained unknown.
The researchers discovered a cluster of neurons in the hypothalamus that express the receptor for the inhibitory neurotransmitter GABA (Gamma-Aminobutyric Acid). This cluster, known as the GABRA5 cluster due to its association with the α5 subunit of the GABAA receptor, appears to act as a switch for weight regulation.
Experiments using a diet-induced obese mouse model revealed that inhibiting the activity of the GABRA5 neurons resulted in fat accumulation and weight gain, while activating these neurons led to successful weight reduction.
Unexpectedly, the research team discovered that astrocytes in the lateral hypothalamus regulate the activity of the GABRA5 neurons. Reactive astrocytes increase in number and size and overexpress the enzyme MAO-B (Monoamine Oxidase B), which influences GABA secretion and inhibits the GABRA5 neurons.
By suppressing the expression of the MAO-B gene in reactive astrocytes, the researchers were able to decrease GABA secretion, reversing the inhibition of the GABRA5 neurons. This resulted in increased heat production in fat tissue, leading to weight loss even while consuming a high-calorie diet.
The researchers also tested a selective and reversible MAO-B inhibitor called KDS2010 on obese mice. The drug demonstrated significant results, reducing fat accumulation and weight without impacting food intake.
This discovery brings hope to the one billion individuals worldwide struggling with obesity. Obesity has been designated by the World Health Organization as the “21st-century emerging infectious disease.” The researchers believe that KDS2010 could be a next-generation obesity treatment that effectively combats obesity without suppressing appetite.
Further research is needed, but the potential implications of this groundbreaking discovery are immense. By understanding the role of astrocytes and the GABRA5 cluster in weight regulation, scientists are one step closer to developing effective treatments for obesity.