Food intake and energy utilization are significantly influenced by endocannabinoids in the brain. Researchers from the University of Montreal affiliated hospital research center (CRCHUM) believe that altering the way these molecules function could aid in the fight against obesity.
According to the source, Stephanie Fulton, a medical professor at the University of Montreal, and her colleagues have spent years figuring out how the human neurological system regulates hunger, physical activity, and mood, as well as how metabolism impacts mood. Their most recent finding, which was reported in Nature Communications, expands on that understanding.
First co-authors Stephanie Tobin, a former postdoctoral fellow, and David Lau, a doctoral student at the University of Montreal, demonstrate in their study that neurons in the nucleus accumbens, a part of the brain rich in endocannabinoids that aids in controlling food reward and physical activity, strongly modulate body-weight control in mice.
2-arachidonoylglycerol (2-AG), a crucial endocannabinoid molecule, is broken down in the brain by the enzyme ABHD6. When the team led by Marc Prentki, a researcher at the CRCHUM, discovered in 2016 that whole-body inhibition of ABHD6 decreased body weight and prevented diabetes, it raised the question of what this enzyme does in the brain to influence appetite and body weight.
Fulton stated, “There was less motivation for food and greater interest in physical activity when we deleted the gene encoding ABHD6 in the nucleus accumbens in mice. This was a surprising discovery as we expected that increasing 2-AG levels would stimulate food intake by increasing cannabinoid signaling.”
“In contrast to the control group, which grew fat and listless, the mice choose to spend more time on a running wheel.” Her team was able to fully shield mice against weight gain and obesity by injecting a specific ABHD6 inhibitor into their brains.
Can have opposite effects
Today’s scientists must be able to target particular brain neural pathways in order to regulate weight. The consequences of blocking ABHD6 can vary depending on the part of the brain that is being targeted.
In 2016, Fulton and Thierry Alquier, a colleague at CRCHUM, demonstrated that mice were resistant to weight loss when ABHD6 was blocked in specific hypothalamus neurons.
However, the authors of the new study demonstrate that inhibiting this chemical throughout the brain reduces weight gain when following a high-fat diet.
No signs of anxiety
According to Fulton, “we also demonstrate in our study that mice with the ABHD6 gene suppressed do not exhibit indications of anxiety and depressive behaviour.”
This is significant since the weight-loss medication Rimonabant, which targeted cannabinoid receptors in the central nervous system, was taken off the market in the late 2000s after users had severe side effects, including suicidal thoughts and despair.
According to the scientists, Fulton’s team’s most recent research paves the path for treatments to combat metabolic diseases like type 2 diabetes and obesity.
It is unknown if the pathways the researchers are targeting in mice will be the same in people while ABHD6 pharmacological inhibitors are being evaluated.
-NSH Digidesk
