Popular GLP-1 weight-loss drugs such as Ozempic and Wegovy can help people lose significant amounts of weight, but part of that loss may come from muscle. Researchers at Northwestern University have now identified an experimental approach that could potentially reduce this effect.
In a study in mice, scientists found that combining semaglutide, the active ingredient in Ozempic and Wegovy, with an experimental RNA-based therapy helped the animals lose more body fat while preserving more muscle than semaglutide alone.
The findings were published in the Proceedings of the National Academy of Sciences.
The experimental therapy works by activating thermogenesis, the process through which the body produces heat and burns energy. Researchers targeted a gene called ZFP423, which normally prevents white fat cells from developing into beige fat cells.
White fat primarily stores energy, while beige fat can burn energy and generate heat. By blocking ZFP423, the researchers were able to promote the conversion of white fat into beige fat and increase the body's energy expenditure.
“We have identified, for the first time, an RNA therapy that promotes thermogenesis and, when combined with the GLP-1 drug semaglutide, helps preserve lean muscle mass,” said Dr. Joseph Bass, senior author of the study and director of the Center for Diabetes and Metabolism at Northwestern University Feinberg School of Medicine.
Combination therapy reduced muscle loss in miceThe researchers first tested the RNA therapy on its own. In mice, it improved blood sugar regulation and reduced body fat without causing measurable muscle loss.
The combination with semaglutide produced a stronger effect.
Mice receiving semaglutide alone lost about 10% of their muscle mass. Those treated with both semaglutide and the experimental RNA therapy lost about 5.5%.
The combination-treated animals also had less body fat at the end of the experiment — around 4 grams compared with nearly 8 grams in the semaglutide-only group — and showed improved blood sugar control.
The work builds on several years of research in Bass' laboratory.
Chelsea Hepler, who is now at the University of Michigan, previously investigated the relationship between the body's internal clock and its ability to change between different types of fat. That work followed research by Rana Gupta at Duke University, who identified ZFP423 as a gene involved in blocking the conversion of white fat into beige fat.
Bass' team subsequently collaborated with Ionis Pharmaceuticals, a company specializing in RNA-based medicines, to develop an experimental therapy designed to suppress the gene.
The researchers say the next step is to test the approach in human cells. The study does not yet establish whether the treatment is safe or effective in people.
Northwestern University has filed a provisional patent for the therapy, naming Bass and first author Anneke Thorne as inventors. The research was supported in part by the National Institutes of Health.
Follow NEWS.am Medicine on Facebook and Twitter