Inhibiting Maobi Enzyme in the Brain Activates ‘GABRA5 Neurons’ and Reduces Weight
Researchers at the Institute for Basic Science (IBS) have discovered a groundbreaking method for weight loss that doesn’t require exercise or diet control. Instead, they have found that controlling a type of brain cell called astrocytes can effectively reduce weight. Astrocytes are star-shaped non-neuronal cells that are the most abundant in the brain. The researchers developed a new drug candidate through their study and conducted animal trials to confirm its effectiveness in promoting weight loss.
Led by Lee Chang-joon, a team of researchers at the Center for Cognition and Sociality at IBS, published their findings in the prestigious journal Nature Metabolism. With over 1 billion obese individuals worldwide, obesity is recognized as the underlying cause of various health issues. Traditionally, managing weight involves making lifestyle changes, such as controlling food intake and increasing physical activity. However, this research highlights the potential of regulating astrocytes in the brain to combat obesity.
In the brain, the lateral hypothalamus plays a crucial role in controlling hunger and energy balance in the body. While it is known that the neurons in the hypothalamus are connected to fat metabolism, the exact mechanism has remained elusive. To shed light on this, the research team conducted animal experiments using rats to analyze the lateral hypothalamus. Their findings revealed the presence of a cluster of neurons called GABRA5 in the hypothalamus. Activating these neurons resulted in weight loss, while inhibiting them led to weight gain, establishing GABRA5 as a control switch for weight regulation.
Furthermore, the researchers discovered that the activity of GABRA5 neurons is regulated by astrocytes in the hypothalamus. Abnormalities in astrocytes were found to result in the expression of the MAO-B enzyme, which causes an increase in the production of GABA, an inhibitory neurotransmitter. This excess GABA inhibits the activity of GABRA5 neurons. By inhibiting the expression of the Maobi gene, the researchers were able to reduce GABA levels and reactivate GABRA5 neurons, ultimately leading to weight loss. These findings signify the potential of the Maobi enzyme as an effective target for obesity treatment.
Not content with mere scientific discovery, the research team is collaborating with the bio-company Neurobiogen to develop a substance for obesity treatment. They have already developed a Maobi inhibitor called ‘KDS2010’ and are currently conducting animal trials to further evaluate its efficacy.
Director Lee Chang stated, “Obesity poses a significant threat to the health of modern society, to the extent that the World Health Organization (WHO) classifies it as a new infectious disease of the 21st century and one of the top 10 health risk factors worldwide. Our goal is to develop effective obesity treatments that don’t rely on appetite suppression.”
The regulation of fat metabolism in astrocytes (mimetic diagram) – Photo: Institute of Basic Science (IBS)
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Reporter Kim In-han, Money Today | 2023.09.01 00:00
Inhibiting the Maobi enzyme in the brain activates ‘GABRA5 neurons’ and reduces weight
Researchers at the Institute for Basic Science (IBS) have found that weight loss can be achieved by controlling astrocytes in the brain, not through exercise or diet control. / Photo = Getty Image Bank Researchers in Korea have discovered that weight loss can be achieved by controlling the ‘Astrocyte’ in the brain, not through exercise or diet control. Astrocytes are star-shaped non-neuronal cells that occupy the largest number in the brain. Specifically, the new drug candidate developed through this study was administered to animals to directly confirm the diet effect.
According to the scientific community on the 1st, Lee Chang-joon’s research team at the Center for Cognition and Sociality at the Institute for Basic Science (IBS) published a research paper on the same day in the international journal Nature Metabolism.
There are over 1 billion obese people worldwide. Obesity is caused by an increase in fat tissue in the body and is known as the root of all disease. To overcome obesity, you need to improve your lifestyle to control your food intake or increase your exercise. However, a research team in Korea published a thesis stating that obesity can be overcome by regulating astrocytes in the brain, attracting attention.
In our brain, the lateral hypothalamus controls the normal hunger and energy balance in the body. Meanwhile, neurons in the hypothalamus are known to be connected to adipose tissue and involved in fat metabolism, but the clear mechanism for this has not been identified.
Therefore, the research team conducted an animal experiment using rats to analyze the lateral hypothalamus. As a result, they found a cluster of neurons, GABRA5, in the hypothalamus. Then, it was confirmed that when GABRA5 neurons were activated, weight decreased, and when it was inhibited, weight increased. This means that GABRA5 neurons are pressure control switches.
Specifically, the research team found that astrocytes in the hypothalamus regulate the activity of GABRA5 neurons. In addition, when astrocytes broke the homeostasis of the brain abnormally and increased in number and size, the enzyme MAO-B was expressed. In this way, large amounts of GABA, an inhibitory neuron substance, were produced, inhibiting the activity of GABRA5 neurons.
Through this, the research team revealed that inhibiting Maobi gene expression reduces GABA and ultimately activates GABRA5 neurons, leading to weight loss. This is a result of experimentally identifying the fact that the ‘Maobi enzyme’ can be an effective target for obesity treatment.
The research team does not stop with a simple scientific discovery, but develops a substance to treat obesity by transferring technology to the bio-company Neurobiogen. In particular, he has developed ‘KDS2010’, a Maobi inhibitor, and is currently conducting animal experiments.
“Obesity is a serious threat to the health of modern people to the extent that the World Health Organization (WHO) classifies it as a new infectious disease of the 21st century and designates it as one of the world’s top 10 health risk factors,” he said. Director Lee Chang “We hope that effective obesity treatment can be achieved without suppressing appetite.”
Mimetic diagram of the regulation of fat metabolism in astrocytes. / Photo = Institute of Basic Science (IBS)
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