Obesity touches countless lives across the country and can lead to many other health complications. From August 2021-2023, the prevalence of obesity in adults in the U.S. was more than 40% . Recently published research led by scientists at VCU Massey Comprehensive Cancer Center found that targeting fat cells specifically with sphingosine kinase 2 inhibitors 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 it, 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.”
About obesity and cancer
Fat tissue produces excess amounts of estrogen. High levels of estrogen have been associated with increased risks of breast, endometrial, ovarian and some other cancers.
People with obesity often have increased blood levels of insulin and insulin-like growth factor-1 (IGF-1), which are both associated with increased risks of colorectal, thyroid, breast, prostate, ovarian and endometrial cancers.
People with obesity often experience chronic inflammation, which promotes tumor growth.
Fat cells (adipocytes) produce hormones called adipokines, which can influence cell growth.
Obesity can also worsen aspects of cancer survivorship , such as quality of life, cancer recurrence, cancer progression, prognosis and risk of second primary cancers.
The research findings
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, fat accumulation in multiple adipose depots, and 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.
What is sphingosine kinase 2 (SPHK2)?
SPHK2 is an enzyme that creates sphingosine 1-phosphate, which is a bioactive molecule that has both intracellular and extracellular signaling roles.
It has been shown to be involved in many types of cancer, particularly of the liver, and inflammation.
In various models, SPHK2 was found to either promote or slow down tumor growth depending on the type of tissue involved.
What’s next?
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.”
Collaborators
Lead author: Ryan D. R. Brown
Massey research members: Katarzyna Tyc, Ph.D., Christopher Green, Ph.D., Sara Spiegel, Ph.D.
Other VCU collaborators: Cynthia Weigel, Ph.D., Yadu Vijayan, Ph.D., Christiane Carter
This research was funded by:
National Institutes of Health
VCU Accelerate Fund
Science Advances
Sphingosine kinase 2 regulates adipocyte browning and whole-body metabolism
21-Aug-2026