The injection of a tiny capsule containing heat-generating cells into the abdomens of mice led those animals to burn abdominal fat and initially lose about 20 percent of belly fat after 80 days of treatment.
Researchers conducting the study were surprised to see that the injected cells even acted like "missionaries," converting existing belly fat cells into so-called thermogenic cells, which use fat to generate heat.
Over time, the mice gained back some weight. But they resisted any dramatic weight gain on a high-fat diet and burned away more than a fifth of the cells that make up their visceral fat, which surrounds the organs and is linked to higher risk for Type 2 diabetes, cancer and heart disease.
The scientists took advantage of the heat-generating properties of a so-called good fat in the body, brown fat, to cut back on the white fat cells that compose the visceral fat that tends to accumulate in the belly.
The scientists combined those brown fat thermogenic cells with genetically modified cells missing an enzyme that leads to visceral fat growth. The engineered cells were placed inside a gel-like capsule that allowed for release of its contents without triggering an immune response.
"With a very small number of cells, the effect of the injection of this capsule was more pronounced at the beginning, when the mice dramatically lost about 10 percent of their weight. They gained some weight back after that. But then we started to look at how much visceral fat was present, and we saw about a 20 percent reduction in those lipids. Importantly, other nontreated peripheral or subcutaneous fat, which has some beneficial health effects, remained the same. That's what we want," said Ouliana Ziouzenkova, assistant professor of human nutrition at Ohio State University and lead author of the study.
"We observed the mice for 80 days after injection and the capsule didn't break or cause any scarring or inflammation. This suggests it's a clean, safe potential therapy for obesity," added Ziouzenkova, also an investigator in Ohio State's Comprehensive Cancer Center and the Center for Clinical and Translational Science. Studies in larger animals would be needed before trials in humans could begin, she said.
If this were someday approved for humans, Ziouzenkova said such a therapy would be best suited to patients who develop visceral fat with aging, aren't able to exercise and shouldn't dramatically reduce their calories because that can cause the loss of beneficial subcutaneous fat. She also noted that anti-obesity drugs for humans currently on the market can reduce body weight by about 10 to 15 percent, but also have side effects.
The research is published in a recent issue of the journal Biomaterials.
A year ago, Ziouzenkova's lab identified an enzyme in mice that relates to fat accumulation after consumption of a high-fat diet, and she recently published a paper indicating that mice lacking that enzyme could stay lean even while eating excess fat. She applied those findings in this work by using the genetically modified cells that are missing that enzyme to potentially help boost the ability of brown fat cells to burn up visceral fat.
For this study, she collaborated with Ohio State chemists to create the capsules. They are composed of alginate-poly-L-lysine, a compound that creates enough of a barrier to encapsulate cells without signaling the immune system that it should react to a foreign object in the body, while also enabling nutrient supply to the encapsulated cells for their long-term survival.
The researchers used three groups of normal mice for the study, feeding them all a high-fat diet for 90 days. After that, five mice received no treatment, five were treated with empty capsules and five received an injection of active capsules containing genetically engineered cells. The capsules were injected into two areas of visceral fat in their abdomens.