Brain Enzyme could Revolutionize Obesity Treatment
Researchers at the Université de Montréal’s affiliated hospital research center (CRCHUM) have made a significant breakthrough in the fight against obesity. Their findings, published in Nature Communications, highlight the crucial role of endocannabinoids in the brain’s regulation of food intake and energy expenditure. Manipulating these molecules, they suggest, could offer a novel approach to combating this widespread health issue.
For years,Professor Stéphanie Fulton and her team have investigated the intricate neural mechanisms governing appetite,physical activity,and metabolism’s impact on mood. Their latest research delves deeper into these processes, focusing on the nucleus accumbens, a brain region rich in endocannabinoids that plays a key role in reward and activity levels.
The study, led by doctoral student David Lau and former postdoctoral fellow Stephanie Tobin, demonstrates that body weight in mice is significantly influenced by neurons within the nucleus accumbens.Specifically, the enzyme ABHD6, which breaks down the endocannabinoid 2-arachidonoylglycerol (2-AG), plays a critical role.
Building on a 2016 discovery by the CRCHUM’s Marc prentki’s team showing that whole-body ABHD6 inhibition reduced weight and protected against diabetes, Fulton’s team sought to understand the enzyme’s brain-specific effects. “We expected that increasing 2-AG levels woudl stimulate food intake,” explained Fulton, ”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.”
“The mice chose to spend more time on a running wheel as compared to the control group which became obese and lethargic,” she added. Furthermore, targeted ABHD6 inhibition in the brains of mice wholly prevented weight gain and obesity.
Targeting the Brain for Weight Management
The ability to precisely target specific brain pathways for weight control represents a major advancement. The researchers found that inhibiting ABHD6 can have contrasting effects depending on the brain region targeted. Previous work by Fulton and colleague Thierry Alquier showed that blocking ABHD6 in certain hypothalamic neurons made mice resistant to weight loss. However, this new study reveals that broader brain inhibition of ABHD6 effectively reduces weight gain on a high-fat diet.
Importantly, the researchers observed no signs of anxiety or other negative side effects in the mice treated with the ABHD6 inhibitor. This suggests a potential for developing safe and effective therapies for obesity based on this mechanism.
this research opens exciting avenues for developing new treatments for obesity, a condition affecting millions in the U.S. The findings underscore the complex interplay between the brain and body weight, offering hope for future therapies that target specific neural pathways to promote healthy weight management.
New Hope in the Fight Against Obesity: A Breakthrough in Understanding Metabolic Disorders
Researchers have made a significant breakthrough in understanding the link between a specific gene and obesity, possibly paving the way for new treatments for obesity and related metabolic disorders like type 2 diabetes. The findings, published recently in nature Communications, suggest that inhibiting the gene encoding ABHD6 could offer a novel approach to combating weight gain and its associated health risks.
The study, conducted on mice, revealed a surprising connection. “Mice in which the gene encoding ABHD6 has been inhibited do not show signs of anxiety and depressive behavior,” explained lead researcher Dr. fulton. This is a crucial finding,especially considering the history of rimonabant,a weight-loss drug withdrawn from the market in the late 2000s due to significant side effects including depression and suicidal thoughts. The earlier drug targeted cannabinoid receptors in the central nervous system, highlighting the potential dangers of targeting the wrong pathways in weight management.
This new research offers a more nuanced approach. By focusing on ABHD6, the scientists believe they’ve identified a potential target for therapies that could effectively combat obesity without the concerning psychological side effects seen with Rimonabant. The implications for millions of Americans struggling with obesity and its related health complications are ample.
The team’s work is still in its early stages. While researchers are currently screening ABHD6 drug inhibitors, the next step is to determine if the mechanisms observed in mice translate effectively to humans. Further research is needed to confirm the efficacy and safety of this approach in human clinical trials. However, the initial findings are undeniably promising and represent a significant step forward in the ongoing battle against obesity and its devastating consequences.
The high prevalence of obesity and type 2 diabetes in the United States underscores the urgent need for innovative treatment strategies.This research offers a glimmer of hope, suggesting a potential avenue for developing safer and more effective therapies to address this critical public health challenge. The potential impact on reducing healthcare costs associated with obesity-related illnesses is also significant.
The study, “ABHD6 loss-of-function in mesoaccumbens postsynaptic but not presynaptic neurons prevents diet-induced obesity in male mice,” was published in Nature Communications in 2024. [Linktothestudy:[Linktothestudy:https://doi.org/10.1038/s41467-024-54819-5]
