Study senior author Joseph Bass in his lab at Northwestern Medicine in Chicago. Credit: Northwestern University
An experimental RNA therapy that triggers the body to burn calories helped mice lose more weight and fat while preserving muscle when combined with the GLP-1 drug semaglutide. The therapy is a potential solution to a common drawback of losing muscle mass when taking a GLP-1 treatment.
For the study, published in the Proceedings of the National Academy of Sciences, researchers focused on a small strand of RNA that silences a gene called ZFP423, which normally acts as a brake on white fat's ability to convert into energy-burning beige fat.
The team first tested the RNA therapy on its own in mice eating standard and high-fat diets, tracking body weight, fat and lean mass, energy expenditure, blood sugar and insulin sensitivity throughout. Even alone, the therapy improved glucose tolerance and reduced body fat without causing muscle loss.
The researchers then combined the therapy with semaglutide and found the pairing produced better results than semaglutide alone: mice receiving both treatments lost just 5.5% of their lean mass compared with about 10% for mice on semaglutide alone. The combination also resulted in less body fat at the end of treatment: 4 grams compared with nearly 8 grams with semaglutide alone.
The team is now working on testing similar RNA therapies in human cells. Northwestern University has filed a provisional patent application related to the experimental RNA therapy.
Data from Northwestern University