Scientists have found a protein that may aid GLP-1 users in maintaining their muscle mass.
- 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 one in eight adultsTrusted Source has
used or is currently using GLP-1 medications, with 38% specifically for weight loss.
However, these drugs do
not distinguish between fat and muscle loss, with muscle accounting for 40% to 60%Trusted Source of total weight loss.
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
How
hunger hormones control growth
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.
Understanding
BCL6 as a regulator in muscle maintenance
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.
Is
a new treatment on the horizon?
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.”
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