- One big area of concern for users of GLP-1 medications such as Ozempic and Wegovy is preventing muscle loss during weight loss.
- Salk Institute researchers have identified that the protein BCL6 is key in maintaining muscle mass.
- Their research in mice revealed that boosting BCL6 levels restores muscle mass and strength, offering hope for GLP-1 users and others prone to muscle deterioration.
- This discovery could lead to innovative treatments for conditions like aging, cancer cachexia, and obesity-related muscle loss while opening new doors for weight management strategies.
In the United States, roughly
However, these drugs do not distinguish between fat and muscle loss, with muscle accounting for
This raises the question: how can we shed pounds without losing essential muscle?
In their study, published in Proceedings of the National Academy of Sciences, scientists revealed that mice with reduced BCL6 levels experienced significant declines in muscle mass and strength while increasing BCL6 effectively restored these losses.
The findings suggest that combining GLP-1 medications with a BCL6-enhancing drug could help prevent muscle loss.
First author Hunter (Hui) Wang, PhD, postdoctoral fellow at The Salk Institute for Biological Sciences, told Medical News Today that their research revealed that “the transcriptional repressor BCL6 is required to maintain muscle mass and strength by regulating muscle gene expression, especially during changes in nutritional status.”
“In simple terms, we found BCL6 helps muscles stay strong by coordinating growth and nutrient signals. When BCL6 level drops, such as during prolonged fasting, muscle starts to lose mass and strength. Conversely, boosting BCL6 levels with gene therapies restores muscle mass and strength in preclinical studies.”
— Hunter (Hui) Wang, PhD
When you go too long without eating, your body enters a fasted state.
During this time, your stomach releases a hormone called ghrelin, which signals your brain that you’re hungry. In response, your brain produces growth hormone.
This hormone plays an important role in maintaining your body’s growth and metabolism by acting on various cells, tissues and organs.
When growth hormone reaches cells, it stimulates the production of a protein called insulin-like growth factor 1 (IGF1), which is essential for muscle growth.
However, the amount of IGF1 produced is tightly regulated by a network of proteins. One of these proteins, SOCS2, slows down the production of IGF1.
If there isn’t enough SOCS2, IGF1 levels can become uncontrollable, leading to conditions like gigantism (excessive growth).
On the other hand, too much SOCS2 reduces IGF1 levels, resulting in smaller body size and weaker muscles.
While SOCS2 is an important part of the process, it is not the whole story.
Scientists at the Salk Institute wanted to learn more about how growth hormone and IGF1 affect muscle maintenance, especially to prevent rapid muscle loss.
By analyzing a large database of human tissue samples, they found that muscle cells contain high levels of a protein called BCL6, suggesting it may also play a significant role in regulating muscle health and strength.
This research provides new insights into how various factors control muscle growth and maintenance, which could help develop better ways to prevent muscle loss in the future.
To investigate BCL6’s role in muscle maintenance, researchers compared mice with and without functional BCL6 proteins.
Mice lacking BCL6 showed a 40% reduction in muscle mass compared to healthy mice, and their remaining muscle was structurally and functionally impaired.
However, increasing BCL6 expression in the muscles of these mice successfully restored both muscle mass and strength.
In addition, when normal mice were compared to those who fasted overnight, the fasting mice had lower BCL6 levels in their muscles.
This demonstrated that BCL6 plays a key role in muscle maintenance.
But how? Further experiments revealed the mechanism at work.
Fasting triggers the release of growth hormone, which reduces BCL6 levels in muscle cells. BCL6 regulates SOCS2, so a decrease in BCL6 leads to a drop in SOCS2.
Under normal conditions, BCL6 ensures proper SOCS2 expression, which, in turn, controls the production of IGF1.
Without BCL6, this regulation breaks down, causing SOCS2 levels to drop so significantly that IGF1 production slows dramatically, resulting in smaller, weaker muscles.
For GLP-1 users aiming to lose weight without sacrificing muscle mass, a BCL6-boosting injectable might become available in the future.
Meanwhile, the researchers intend to explore how prolonged fasting impacts BCL6 levels and muscle maintenance.
Speaking to Medical News Today, senior author and Salk Professor Ronald Evans, PhD said that “maintaining muscle mass is critical to physical strength, metabolic flexibility, and quality of life.”
“This study highlights BCL6 as a potential therapeutic target for muscle loss due to aging, cancer cachexia, obesity and complications from its treatment (e.g., GLP-1 receptor agonists), which opened doors for many patients experiencing muscle wasting.”
— Ronald Evans, PhD
Mark A. Anton, MD, FACS, medical director at Slimz Weightloss, not involved in this research, told MNT that “this study highlights the intricate relationship between muscle mass regulation and nutritional states, potentially offering new insights into muscle preservation strategies during weight loss.”
Mir Ali, MD, board certified general surgeon, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, also not involved in the research, said that “this is an interesting study that shows how complex the body’s mechanisms of muscle regulation, and how the expression of certain chemicals can affect this.”
“Preserving muscle mass when trying to lose fat is very important. Not only is muscle necessary for normal function, having more muscle mass increases energy expenditure and helps keep weight off. If further research can show a way to increase the expression of muscle building chemicals, it may be another adjunct to help people lose weight and preserve muscle.”
— Mir Ali, MD
