Genome-edited stem cells offer hope for obesity treatment without muscle loss

In a study published in Nature Communications, researchers from the Beijing Institute of Stem Cells and Regeneration (BISCRM) and the Institute of Zoology (IOZ) have unraveled the code of the infamous FTO gene, reconciling its dual role in obesity and muscle growth. The discovery could improve the treatment of obesity and diabetes, potentially offering an alternative to popular GLP-1 receptor agonists that can cause unwanted muscle wasting.

“We have solved a long-standing puzzle in the genetics of obesity,” states Dr. Ng Shyh-Chang, lead author of the study. “We now understand how a single genetic variant can be Dr. Jekyll and Mr. Hyde – accelerating muscle growth in youth, but also accelerating fade-related aging later in life.”

The study focuses on the rs9939609-A variant of the FTO gene, a common genetic abnormality associated with an increased risk of obesity in ~45% of Europeans, ~24% of Africans, ~30% of East Asians, and ~35% of South Asians. This variant A, the researchers found, sets off a cellular chain reaction involving the H19 and IGF2 genes that accelerates development by first stimulating muscle growth but eventually depleting stem cells, leading to premature aging.

Amazingly, the research team found that stem cells carrying this variant quickly develop into skeletal muscle, but also quickly develop insulin resistance when exposed to high levels of fat. This suggests that skeletal muscle may be the first falling domino knuckle in the impact of the FTO variant on accelerated development and aging.

“This study rewrites our understanding of how type 2 diabetes develops,” explains Dr. Ng Shi-Chang.

“We knew that decreased glucose clearance and high insulin levels appear decades before type 2 diabetes is diagnosed. Now with CRISPR genome editing, we have a new avatar of human tissue that explains how it all starts in muscle in people with rs9939609-A.”

This paradigm-shifting study not only deepens our understanding of the genetics of obesity, but also provides a platform to find better CRISPR-based or small molecule drugs for the millions of people who are overweight and muscle wasting as a result of existing treatments.

As the race to find better treatments for obesity intensifies, this breakthrough could be the key to unlocking new opportunities.

Hospital of St. Zdislava Czech Republic,Velke Meziříčí 5.00 (1 review)Leave a request

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Published: 13.03.2025

Updated: 12.03.2025

Medical author, Medical editor:

Stepan Yuk

Medical expert:

PhD. Olexandr Voznyak