Brain Enzyme Discovery Opens New Path to Obesity Treatment

Scientists at the University of Montreal have uncovered a surprising twist in the relationship between brain chemistry and weight control. Their research reveals that targeting a specific enzyme in the brain’s reward center not only prevents obesity but also increases physical activity — without the concerning side effects that have plagued previous obesity treatments.

Published in Nature Communications | Estimated reading time: 5 minutes

In a breakthrough that challenges conventional understanding of appetite control, researchers have found that reducing the activity of an enzyme called ABHD6 in a specific brain region leads to remarkable changes in behavior and metabolism. The study, led by Professor Stephanie Fulton at the University of Montreal Hospital Research Centre (CRCHUM), reveals how precise targeting of brain circuits could offer new possibilities for treating obesity.

“We expected that increasing 2-AG levels would stimulate food intake by increasing cannabinoid signalling, but paradoxically found that when we deleted the gene encoding ABHD6 in the nucleus accumbens in mice, there was less motivation for food and greater interest in physical activity,” explains Fulton.

The research team’s findings are particularly significant because they overturn previous assumptions about how endocannabinoids – natural compounds similar to those found in cannabis – influence appetite and activity levels. When they removed the ABHD6 enzyme from a brain region called the nucleus accumbens, mice became more active and resistant to weight gain, rather than showing the expected increase in appetite.

This discovery builds on the team’s 2016 research, which first identified ABHD6’s role in body weight regulation. The new study demonstrates that targeting this enzyme in specific brain areas can have dramatically different effects. Most importantly, unlike previous weight-loss drugs that targeted similar systems, this approach showed no signs of causing anxiety or depression in the test subjects.

By injecting an ABHD6 inhibitor directly into the brains of mice, the researchers achieved complete protection against obesity. This precision targeting appears to be crucial – the team found that inhibiting ABHD6 in different brain regions can produce opposite effects on weight control.

While these results are promising, the researchers emphasize that additional work is needed to determine whether these mechanisms function similarly in humans. The research team, including first co-authors David Lau and Stephanie Tobin, continues to investigate how these findings might translate into therapeutic applications.

Glossary

Endocannabinoids Natural compounds produced in the body that help regulate various functions, including appetite and metabolism. ABHD6 An enzyme in the brain that breaks down endocannabinoids, influencing how they affect behavior and metabolism. Nucleus Accumbens A region of the brain involved in reward and motivation, playing a crucial role in food-related behaviors and physical activity.

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