Gene’s role in achieving and maintaining muscle mass revealed in new study

New research from Northwestern University has discovered a previously unexplored relationship between a gene essential to immune cells and the establishment and maintenance of skeletal muscle mass and strength in mice.

We know that the BCL6 gene plays a key role in the functioning of immune cells and in the body’s inflammatory response. For decades, scientists have also known that the gene is highly expressed in skeletal tissue, but until now its function in this metabolic tissue was unknown.

“Usually when genes are expressed at high levels, it implies an important function,” said final author Dr. Grant D. Barish. “The study was undertaken with the idea that the gene was doing something important in skeletal tissue, but we didn’t know what.”

Barish is the Martha Leland Sherwin Professor of Medicine in the Division of Endocrinology at Northwestern University Feinberg School of Medicine, as well as a practicing clinician. He is affiliated with the Center for Diabetes and Metabolism and the Simpson Querrey Institute for Epigenetics.

He is also a member of the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. Barish has been interested in the BCL6 gene, which codes for a transcription factor, for more than a decade, primarily to understand its impact on diabetes and other endocrine disorders.

The study was published last week in Natural metabolism.

The team used several strategies to explore the function of the gene, including deleting the gene in utero to see the impact on preformed muscle tissue and deactivating the gene in adult mice, which resulted in a rapid loss of muscle tissue. muscular mass. Mice born without the BCL6 genes were chewed and grew muscles that were reduced in mass by 30%. Interestingly, even after development, in adult mice, the gene had a large impact on the ability to maintain muscles.

“The results were completely consistent and this is a robust effect that suggests a novel function of this gene that has primarily been studied in the immune system, but this appears to be a very important change in the control of muscle mass” , Barish said.

When muscle mass falls outside of a normal range, it results from a breakdown in the delicate balance the body maintains between protein synthesis and breakdown. When protein synthesis is affected, typically one step in the protein expression process – transcription or translation – is out of balance. However, in the case of BCL6, scientists discovered a dual function. Using ribosomal sequencing, they discovered that the gene not only controls transcription, but also some of its regulated genes that control translation.

The gene also appears to impact protein degradation. “There is decreased synthesis and greater degradation,” Barish said. “So between the two, the net effect is a reduction in muscle mass when BCL6 is lost.”

Barish said his study paves the way for a mechanism to be explored in relation to conditions that cause muscle wasting, such as nerve damage, nutrient deficiencies, cancer and immobility, all conditions for which treatments are lacking. specific medical treatments for muscle loss. Cancer and nutritional insufficiency lead to reductions in BCL6, but more work is needed to understand how they influence each other.

Losing muscle mass is associated with worsening diabetes and insulin resistance, and one reason people become more insulin resistant and more diabetic as they age is that they lose muscle mass.

People who lose muscle mass also become weaker with aging and are more susceptible to falls and fractures that land them in the care of an orthopedist.

Muscle mass has a direct impact on other disease states, quality of life, and morbidity and mortality, but there is no therapeutic treatment for muscle loss. Barish said there is still much to understand about how muscle mass is controlled at the molecular level and his approaches are starting to open doors.