University of Massachusetts Amherst researchers have identified an enzyme that might be responsible for increased colon inflammation in obese people — and they’re hoping that, by inhibiting it, they might someday prevent colon cancer.
It’s widely known that obese people are at a greater risk of colon cancer, but the mechanisms aren’t well understood, said Guodong Zhang, a food science professor at UMass Amherst.
The researchers found that an enzyme called soluble epoxide hydrolase, or sEH, which is more abundant in the colons of obese people, is responsible for colin inflammation, which can be an early signal of colon cancer.
UMass researchers, along with colleagues from University of California, Davis, collaborated on the study which was published Monday in the journal PNAS.
The next step was coming up with a way to inhibit sEH, which is also known to cause other diseases, including hypertension and general inflammation, Zhang said.
The team used two different drugs — TPPU and t-TUCB, developed by Professor Bruce Hammock’s lab at UC Davis — to block sEH, testing them out in obese mice. They found that even low doses of the drugs led to a significant decrease in colon inflammation in obese mice.
“We think obesity-enhanced colon inflammation and associated colon cancer is a very serious, unmet medical problem, and now we have a new strategy to potentially control this issue,” Zhang said.
The enzyme produces fatty acid compounds associated with colon inflammation, Zhang said. High saturated animal fats in “typical Western diets” have been reported to directly enhance sEH expression, but there’s still limited research on why the enzyme is more abundant in obese subjects, he said.
Researchers also used genetically-modified mice that could not produce sEH — and found they experienced dramatically reduced colon inflammation even when the mice became obese.
Several pharmaceutical companies are already in the process of developing sEH inhibitors for human trials for other conditions. Zhang said his team is hoping those drugs could be repurposed to stop obesity-induced colon inflammation and ultimately prevent obesity-enhanced cancer.
More than one-third of adults in the United States are obese, according to the Centers for Disease Control and Prevention, and obese individuals are about 30 percent more likely to develop colon cancer, one of the most common cancers in the nation, according to statistics from the National Cancer Institute and the American Cancer Society.
“Obesity is already a very serious problem in the United States,” he said. “This is how we can reduce diseases related to obesity.”Elise Takahama can be reached at firstname.lastname@example.org. Follow her on Twitter @elisetakahama.