Targeting fat-cell enzyme offers potential strategy to reduce obesity and cancer risk
· Medical Xpressby Virginia Commonwealth University
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Obesity touches countless lives across the country and can lead to many other health complications. From August 2021 to 2023, the prevalence of obesity in adults in the U.S. was more than 40%. Research published in Science Advances, led by scientists at VCU Massey Comprehensive Cancer Center, found that targeting fat cells specifically with inhibitors of the enzyme sphingosine kinase 2 could be a new strategy to combat obesity and lower the risk of its comorbidities like cancer.
"GLP-1s are well established to help reduce body weight. However, they don't work for everyone. And once you stop taking them, the weight may come back," said Christopher Green, Ph.D., study co-author and member of the Cancer Biology research program at Massey.
"So, there is a need to develop additional therapies, and we think that targeting adipocytes with sphingosine kinase 2 inhibitors could be a new strategy to treat people with obesity and affect their susceptibility to developing cancer."
Targeting SPHK2 in fat cells
In previous studies, Green and his research team found that whole-body deletion of sphingosine kinase 2 (SPHK2) led to protection from Western diet–induced obesity and fat accumulation in multiple adipose depots, as well as reduced liver cancer in male mice.
After targeting SPHK2 in the adipocytes in these models during this study, they determined that there was a significant reduction in body weight, improved glucose tolerance, improved insulin sensitivity and reduced lipid accumulation in the liver.
These initial results led them to believe that targeting adipocytes specifically with sphingosine kinase 2 inhibitors could be a new strategy to reduce the risk of cancers that stem from obesity.
More precise inhibitors remain a goal
Moving forward, the team plans to continue to explore the role of SPHK2 in obesity and cancer, and they are hopeful more specific inhibitors will be developed that solely target SPHK2, as current inhibitors on the market have off-target effects.
"Additionally, future therapeutic strategies designed to more precisely target specific fat depots will be immensely beneficial," said Green. "By localizing treatment, these strategies can reduce obesity and its comorbidities—including cancer—while minimizing unwanted side effects."
Publication details
Ryan D. R. Brown et al., Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism, Science Advances (2026). DOI: 10.1126/sciadv.aec7066
Journal information: Science Advances
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Weight managementOncologyEndocrinologyClinical pharmacology Provided by Virginia Commonwealth University Who's behind this story?
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