A brain 'switch' that prevents obesity has been discovered. An international joint research team successfully reduced appetite and increased motivation for exercise by inhibiting a specific enzyme in the brain. This method has been evaluated as opening a new path for obesity treatment without side effects, unlike existing obesity medications.
Researchers at the Montreal Clinical Research Center (CRCHUM) at McGill University in Canada noted on the 16th that they revealed the principle of treating obesity by inhibiting the enzyme 'ABHD6.' The research results were published in the international journal 'Nature Communications' on the same day.
The research team has been studying how the brain regulates appetite and physical activity. In 2016, they discovered that inhibiting an enzyme called ABHD6 was effective for weight loss and diabetes prevention. Through this study, the research team aimed to investigate the process by which the ABHD6 enzyme is involved in weight regulation.
According to the study, the part of the brain that plays a crucial role in weight regulation was identified as the nucleus accumbens. The nucleus accumbens regulates the pleasure experienced when eating and the motivation for exercise. In this area, the ABHD6 enzyme breaks down the endocannabinoid molecule 2-arachidonoylglycerol (2-AG), and the more this process is inhibited, the more weight decreases. Endocannabinoids are substances naturally produced in the brain and body, regulating various physiological processes, including appetite, mood, and motivation for exercise.
The research team conducted animal experiments to observe the changes occurring when the ABHD6 enzyme was inhibited. As a result, mice with the ABHD6 enzyme gene inhibited showed reduced appetite and moved more actively on the exercise wheel. In contrast, mice with normally functioning enzyme genes overate and became obese. Additionally, they were able to prevent weight gain by injecting an ABHD6 inhibitor into mice consuming high-fat diets.
In particular, the effect of inhibiting ABHD6 varied depending on specific areas of the brain. Previous studies found that blocking this enzyme in the hypothalamus made it difficult to reduce weight, but this study confirmed that inhibiting the ABHD6 enzyme throughout the brain effectively prevented weight gain.
This study shows the potential to solve the problems of existing obesity treatments. Previous cannabinoid-based obesity medication 'rimonabant' had weight loss effects but was withdrawn from the market due to serious side effects such as anxiety, depression, and suicidal impulses. However, mice treated with the ABHD6 inhibitor showed no side effects such as anxiety or depression at all.
The research team stated, 'The results of this study could be of great help in treating diseases such as obesity and diabetes,' adding, 'Further studies are needed to verify whether the results observed in mice will also appear in humans.'
References
Nature Communications (2024), DOI: https://doi.org/10.1038/s41467-024-54819-5