Summary: A recent study reveals that modifying the brain’s endocannabinoids can lower blood sugar and promote physical activity, making overweight a tempting option. Scientists discovered that inhibiting the nucleus accumbens enzyme ABHD6 reduced animal’s appetite for food while boosting their desire to exercise.
This method didn’t show any signs of anxiety or depression in the mice, unlike past weight-loss medications. Although more research is required to ensure similar effects in people, these findings may lead to safer treatments for obesity and metabolic problems like type 2 diabetes.
Major Information
- ABHD6 Role: Blocking ABHD6 in the mind reduced food enthusiasm and promoted physical exercise.
- No anxiety or depressed behavior was observed in animals after ABHD6 was inhibited.
- Obesity Treatment Potential: Findings was link safer treatment for obesity and physiological problems.
Origin: University of Montreal
Endorphins in the brain are crucial for regulating food consumption and energy usage. Modulating the action of these molecules could help fight obesity, say researchers at Université de Montréal’s affiliated hospital research centre ( CRCHUM).
For decades, Université de Montréal health professor , Stephanie Fulton , and her crew had been unravelling the systems in the human nervous system that control people’s have to eat and to engage in physical activity, and how their digestion affects their feelings.
Their latest finding, published in , Nature Communications, takes that knowledge a step further.
In their research, first co-authors David Lau, an Université de Montréal graduate student, and Stephanie Tobin, a former doctoral fellow, show that body-weight power in mice is highly modulated by neurons in the nucleus accumbens, a region of the brain that’s rich in endocannabinoids and that helps control food praise and physical activity.
In the head, the enzyme , ABHD6 degrades a crucial cannabinoid molecule known as 2-arachidonoylglycerol (2-AG ).
What does this protein in the mind do in the brain that affects hunger and body mass? The team of Marc Prentki, a scientist at the CRCHUM, discovered this in 2016 and found that whole-body inhibition of ABHD6 reduced body weight and protected against diabetes.
We anticipated that increasing 2-AG levels would increase cannabinoid signaling, but we paradoxically discovered that mice with the deletion of the gene encoding , ABHD6 had less appetite for food and more interest in physical activity, according to Fulton.
” The mice chose to spend more time on a running wheel than the control group, who became fat and lethargic.
Her team was able to completely protect them from weight gain and obesity by injecting a targeted ABHD6 inhibitor into the mice’s brains.
Can have opposite effects
Today, it is crucial for scientists to be able to target particular brain neuronal pathways to control weight. Depending on the area of the brain targeted, inhibiting ABHD6 can have opposite effects.
Fulton and her CRCHUM coworker Thierry Alquier discovered that mice were resistant to losing weight by blocking ABHD6 in some hypothalamic neurons in 2016.
In the current study, however, the authors show that brain-wide inhibition of this molecule has a net effect of diminishing weight gain on a high-fat diet.
No signs of anxiety
” In our study, we also show that mice in which the gene encoding , ABHD6 has been inhibited do not show signs of anxiety and depressive behaviour”, said Fulton.
This is crucial given that Rimonabant, a weight-loss medication that targeted cannabinoid receptors in the central nervous system, was discontinued in the late 2000s after users reported severe side effects like depression and suicidal tendencies.
Fulton’s team’s latest work helps pave the way for therapies to fight obesity and metabolic disorders such as type , 2 diabetes, the scientists believe.
While ABHD6 drug inhibitors are being tested, it is still to be seen whether the research’s methods for treating mice will be the same as those used in humans.
Funding: Funding was provided by the Canadian Institutes of Health, the Montreal Diabetes Research Center, Diabetes Québec and the Fonds de recherche du , Québec.
The research was supported by the CRCHUM’s small-animal phenotyping and imaging core platforms.
About this news about obesity and neuroscience
Author: Bruno Geoffroy
Source: University of Montreal
Contact: Bruno Geoffroy – University of Montreal
Image: The image is credited to Neuroscience News
Original Research: Open access.
” Abdistrict loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice” by Stephanie Fulton et al. Nature Communications
Abstract
In male mice, ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity.
α/β-hydrolase domain 6 ( ABHD6 ) is a lipase linked to physiological functions affecting energy metabolism. ABHD6 degrades 2-arachidonoylglycerol and modifies cannabinoid receptor signaling.
However, it was not known if its functional role in the mesoaccumbens circuitry was crucial for motivated behavior and was significantly influenced by endocannabinoids.
We demonstrate that male mice’s control of the nucleus accumbens by neuronal ABHD6 is a significant determinant of body weight and reward-directed behavior using three viral techniques.
Contrary to expected outcomes associated with increasing endocannabinoid tone, loss of ABHD6 in nucleus accumbens, but not ventral tegmental area, neurons completely prevents diet-induced obesity, reduces food- and drug-seeking and enhances physical activity without affecting anxiodepressive behaviour.
These effects are brought on by attenuated inhibitory synaptic transmission onto medium spiny neurons, which is how these effects are explained.
Dopamine ventral tegmental area neurons and nucleus accumbens neurons have different effects when it comes to effortful responding for food. Intraventricular infusions of an ABHD6 inhibitor also restrain appetite and promote , weight loss.
Together, these results reveal functional specificity of pre- and post-synaptic mesoaccumbens neuronal ABHD6 to differentially control energy balance and propose ABHD6 inhibition as a potential anti-obesity tool.
