A recent study from the University of Montreal, published in Nature Communications, reveals that inhibiting the enzyme Abhd6 in a specific brain region may reduce hunger and increase physical activity.
The endocannabinoid system plays a crucial role in various brain functions, including movement control, learning, memory, and pain modulation. This research indicates that endocannabinoid activity in certain brain areas is also linked to hunger and physical activity, suggesting a potential target for new obesity therapies.
Endocannabinoids, neurotransmitters produced by the body, interact with the same receptors as plant-derived cannabinoids, such as those found in cannabis, which is used for pain relief and treating Parkinson's tremors. One prominent endocannabinoid in the central nervous system is anandamide, which is broken down by the enzyme Abhd6. Previous research has shown that silencing the gene for this enzyme can alter metabolism and promote weight loss.
Initially, it was believed that inhibiting Abhd6 would increase endocannabinoid levels, heightening appetite and leading to weight gain. However, the Montreal researchers sought to investigate the actual brain activity when Abhd6 is inhibited.
The study focused on neurons in the nucleus accumbens, a hypothalamic area involved in motivation and aversion. Using mice, the researchers disabled the genes responsible for synthesizing Abhd6 in this specific brain region, observing changes in appetite and exercise after a high-calorie diet.
Contrary to expectations, the study found that eliminating the Abhd6 gene in the nucleus accumbens reduced food-seeking behavior and increased interest in physical activity. Mice with inhibited Abhd6 spent significantly more time on a running wheel compared to a control group, which became obese and lethargic.
Previous studies indicated that inhibiting Abhd6 in the hypothalamus led to resistance to weight loss. This suggests that endocannabinoid activity may have different effects depending on the neurons involved. To assess which effect—weight loss or weight gain—was stronger, the researchers conducted tests on generalized inhibition of the enzyme throughout the brain, finding that it favored the weight loss effect in mice.
Inhibiting Abhd6 presents an intriguing target for developing new obesity treatments. Future research will determine if these findings apply to humans and whether Abhd6 inhibitors are safe for human use. Past cannabinoid receptor medications faced withdrawal due to severe psychiatric side effects, including depression and suicidal thoughts. However, the inhibition of Abhd6 in mice did not produce anxiety or depression-like behaviors, providing researchers with optimism about the potential safety and efficacy of this target for human obesity treatment.