Research News

Cleveland Clinic researchers are investigating the role of a gene to see whether our genetic makeup holds clues about the future success of weight loss efforts.  

A team led by Daniel Rotroff, PhD, is the first to explore neurobeachin (NBEA) within the context of weight loss. Their first step was to explore whether NBEA – previously associated with patients being more likely to eat sweets – played a role in individualized response to glucagon-like peptide-1 receptor agonists (GLP-1RAs), commonly known as GLP-1s. 

Many individuals who have spent years struggling to lose weight are suddenly experiencing weight loss with these new medications, says Dr. Rotroff, the Director of the Center for Quantitative Metabolic Research and the holder of the Eddie J. Brandon Endowed Chair for Diabetes Research. The challenge is that it is not clear to clinicians and researchers why some patients experience these breakthrough results, while others do not lose weight or suffer from unpleasant side effects. 

Dr. Rotroff’s study published in Diabetes, Obesity and Metabolism with a team of researchers from the National Institutes of Health (NIH) found that NBEA is associated with weight loss outcomes of GLP-1 treatment, providing a new perspective on individualized weight loss. 

“This is just the beginning of our research to understand how NBEA influences GLP-1 signaling,” Dr. Rotroff says. “There are opportunities to explore how this gene impacts metabolic health with a potential role in many other disorders, which can lead to further medical advancements.” 

Why does weight loss matter in health?  

Dr. Rotroff, who also serves as Chair for Quantitative Health Sciences, says obesity in the US is an epidemic that has seen a consistent increase in the number of people with obesity for decades. 

“Obesity is linked to over 200 comorbidities including, cardiometabolic diseases, musculoskeletal disorders, and cancer,” he explains. “We know that treating obesity can have a direct impact on a patient’s quality of life and long-term health.”  

Previously, the main treatment options for obesity were lifestyle modifications and surgery. Dr. Rotroff says although these options can be effective for patients, as our understanding of obesity as a disease has evolved, we now have new medical options to treat obesity. 

“Obesity is a complex disease that is driven by a combination of factors including genetics, environment and lifestyle,” Dr. Rotroff says. “By identifying how genetics influence obesity we can avoid ineffective treatments, reduce healthcare costs and improve access for those who need it most.” 

Why is NBEA so important? 

NBEA is a massive gene that influences the signals our brain sends to our bodies. The average gene has around 300 bases, while NBEA has 700,000 bases. Researchers are still discovering its role and impact throughout different parts of our body. 

Dr. Rotroff and his team chose to study this gene more closely after reviewing the results of a previous clinical trial in patients with type 2 diabetes. In a questionnaire about diets, there was one main differentiator in patients with a variation in the NBEA gene – they were more likely to eat desserts. The gene was also associated with a preference for sugary food in preclinical research. This earned it the nickname “the sweet tooth gene” among the team members.  

How can a gene influence weight loss?  

The NBEA gene is linked to the part of the brain that controls our feeling of fullness and feeding behaviors. To determine its effect on the effectiveness of GLP-1s, the Rotroff team conducted the largest real-world study of the gene using genetic data from the NIH’s All of Us Program and the UK Biobank. 

To analyze the data, the researchers developed a NBEA score based on patients’ genetic markers. They found that patients with a high NBEA score were 82% more likely to respond well to GLP-1s and experience weight loss. Those with a low score were less likely to lose weight.  

“This work shows how important it is to integrate genetic information into routine obesity management,” says study co-author Marcio Griebeler, MD, Director of the Enterprise Obesity Center. “We are confident that this research lays the foundation for tailoring personalized care instead of a one-size-fits-all approach in the obesity field.”