In the neural circuit observed in the study, astrocytes highly express monoamine oxidase (MAO-B) to synthesize and release GABA. These GABA will be received by GABRA5 neurons, reducing the activity of neurons, and ultimately producing similar symptoms as before. fattening effect. The authors found that the number and volume of astrocytes in obese mice were significantly increased, which means that they produce more GABA to inhibit GABRA5 neurons.
In this series of participants, just regulating any one is expected to prevent weight gain in mice, such as increasing GABRA5 neuron activity, inhibiting astrocytes, or reducing astrocyte GABA release.
In the new study, the authors focused on inhibiting the gene encoding the MAO-B enzyme, which reduces the final output of GABA. They found that silencing this gene or using MAO-B enzyme inhibitors could significantly slow down weight gain in mice. Even if the conditions of the high-fat diet are not changed, the mice will not gain weight if they eat freely, and the heat generated in the adipose tissue will increase.
Among them, the MAO-B inhibitor KDS2010 used in the study has entered Phase 1 clinical trials. The researchers pointed out that many obesity treatments in the past focused more on hypothalamic neurons, but they found that even if they are not nerve cells, they can be used to reduce weight. of. This can be a new strategy for achieving weight loss without affecting your appetite.
The study authors used a high-fat diet to construct a group of obese mice and observed that the electrical activity of GABRA5 neurons in these obese mice was significantly reduced. And if you artificially try to inhibit the neuronal activity of GABRA5, the heat production process of the brown adipose tissue of mice will be weakened, which means that energy consumption will be reduced, and the mice will be more likely to accumulate fat and gain weight. In turn, if GABRA5 neurons are stimulated, mice can easily lose weight.
Researchers view GABRA5 neurons as a switch that controls body weight. However, these neurons do not work alone; they also have cooperative connections with other cells in the brain. For example, astrocytes in the lateral hypothalamus can regulate the activity of GABRA5 neurons. These cells are not neurons. They mainly fill in the spaces between nerve cells and play a supporting role. They also participate in intercellular communication.
We often think that our appetite is determined by our mouth and stomach. If we feel it tastes good, we will eat more. If our stomach is full, we will stop eating. But when we look beyond the surface of appetite, clues ultimately lead to the brain's hypothalamus, the area that tightly controls the complex balance between eating and energy expenditure.
For example, some past studies have found that neurons in the lateral hypothalamus are connected to adipose tissue and can participate in fat metabolism.
In a new study in Nature Metabolism, scientists further explored the relevant mechanisms. They discovered a cluster of specialized neurons in the hypothalamus that express receptors for the inhibitory neurotransmitter GABA. The researchers named these nerve cells GABRA5 based on their properties, which project to surrounding brown and white adipose tissue and are linked to fat metabolism.