A fresh approach to tackling obesity has emerged from research at the University of Montreal’s Hospital Research Centre (CRCHUM), focusing on the critical function of endocannabinoids in managing appetite and energy use.
This discovery opens up potential new avenues for obesity treatment by explicitly manipulating these molecules.
Research Insights
Led by Dr. Stephanie Fulton, a medical professor at Université de Montréal, the research team delved into the complex neuromolecular networks that influence eating habits, physical activity, and how metabolism intertwines with emotional health.
Their insights, recently published in Nature Communications, enhance our understanding of these intricate processes.
At the heart of their work is the nucleus accumbens, a brain region rich in endocannabinoids that plays a key role in regulating rewards and activities.
The researchers—comprising doctoral student David Lau and former postdoctoral fellow Stephanie Tobin—identified the enzyme ABHD6, known for breaking down the endocannabinoid 2-arachidonoylglycerol (2-AG), as a crucial player in appetite control.
Key Findings
Earlier studies by Marc Prentki’s team in 2016 established that inhibiting ABHD6 overall could lead to reduced body weight and improved insulin sensitivity.
This raised intriguing questions about the enzyme’s specific effects in the brain when it comes to managing appetite and body weight.
Fulton pointed out a striking finding: unlike the assumption that increasing cannabinoid signaling from elevated 2-AG levels would lead to higher food intake, deleting the ABHD6 gene in the nucleus accumbens caused the mice to show reduced motivation to eat and greater enthusiasm for physical activities.
These mice preferred to exercise rather than remain stationary, standing in stark contrast to a control group that became less active and gained weight.
In a groundbreaking experiment, the research team administered a targeted inhibitor of ABHD6 directly into the mice’s brains.
The result? These mice successfully avoided weight gain and obesity, clearly demonstrating that specific neuronal pathways can be fine-tuned to manage body weight with different impacts depending on the targeted brain region.
Potential for Future Treatments
Furthermore, past research by Fulton and her colleague Thierry Alquier indicated that inhibiting ABHD6 in specific areas of the hypothalamus could hinder weight loss efforts.
However, the current findings suggest that inhibiting this enzyme more broadly throughout the brain can promote resistance to weight gain, even in the face of a high-fat diet.
Another encouraging aspect of the study showed that mice with suppressed ABHD6 gene expression did not show any signs of anxiety or depressive symptoms.
This is especially significant, given that some previous weight-loss medications targeting cannabinoid receptors have been associated with negative mental health outcomes, including depression and suicidal ideation.
The research team’s results point towards the exciting possibility of developing innovative treatments for obesity and related metabolic diseases, such as type 2 diabetes.
While there is ongoing work to identify specific ABHD6 inhibitors, further studies will be essential to determine whether the mechanisms observed in mice will hold true for human biology.
Source: ScienceDaily