The study suggests that boosting BCL6 levels could help prevent muscle loss in people using GLP-1 medications while they shed fat. This new insight could also benefit older adults, as well as patients suffering from systemic diseases like sepsis or cancer, which can lead to muscle wasting.

Published in the Proceedings of the National Academy of Sciences on January 22, 2025, the study demonstrated that mice with lower levels of BCL6 experienced significant reductions in muscle mass and strength. Interestingly, when BCL6 levels were increased, these negative effects were reversed, restoring muscle health. This discovery offers new potential for combining GLP-1 weight loss drugs with BCL6-boosting therapeutics, which could effectively protect muscle mass during fat loss.

“Our research highlights how the body maintains muscle tissue in balance with nutrition and energy levels, shedding light on how we can develop treatments for those losing muscle due to weight loss, aging, or illness,” said Ronald Evans, professor and director of the Gene Expression Laboratory at Salk Institute. “Muscle is the most abundant tissue in the human body, so keeping it healthy is essential to overall well-being.”

Through a series of experiments, the research team discovered that fasting leads to increased secretion of growth hormone, which in turn lowers BCL6 levels in muscle cells. BCL6, a crucial regulator of SOCS2, controls how much IGF1—an important protein for muscle growth—is produced. In the absence of BCL6, IGF1 production significantly decreased, leading to muscle weakening and shrinkage.

The findings point to the potential of combining BCL6-boosting therapies with GLP-1 drugs to counteract unwanted muscle loss, offering a new approach to weight loss treatments and providing a promising solution for individuals prone to muscle loss. As researchers continue to explore the link between muscle health and metabolic pathways, the study opens new doors for therapeutic interventions aimed at preserving muscle function and strength across various patient populations.

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