Fat does a better job of turning up the metabolic heat, and lessening the risks associated with obesity and diabetes, if it has a favorable balance of energy-storing fat and energy-burning fat. If that favorable balance doesn’t exist naturally, it can be engineered, a new study suggests.
The study, completed by scientists from the University of California, Berkeley, tested a new technique for coaxing stem cells to develop into energy-burning beige fat instead of energy-storing white fat. Beige fat, which is also called brown-like fat, forms within white-fat tissue after exposure to cold. Brown fat, which is especially dark because it contains the highest levels of darker-hued mitochondria, arises during fetal development.
White-fat stem cells, the Berkeley researchers knew, can give rise to beige-fat cells under controlled circumstances, mainly the rigidity of the surrounding environment. If the surrounding environment is soft, white-fat stem cells encounter little resistance as they grow, and they eventually form ordinary white-fat tissue. At the other extreme, a very stiff three-dimensional environment, stem cells grow into bone tissue.
Intermediate stiffness, such as that provided by a hydrogel—a sort of three-dimensional matrix that can enmesh cells—encourages stem cells to produce beige fat. A still-firming hydrogel mixed with stem cells, the Berkeley researchers reasoned, could be injected into the body. Then, once inside the body, the hydrogel could continue to thicken, until it enmeshed the stem cells, providing just the right amount of stiffness.
The Berkeley researchers, led by Andreas Stahl, an associate professor of nutritional sciences and toxicology, tried this approach with mice. They made sure that they would be able to keep track of the injected stem cells by engineering them to express a luminescent enzyme from fireflies.
The implants were engineered not only to glow, but to support the differentiation of white fat derived multipotent stem cells into lipid-accumulating, uncoupling protein 1 (UCP1)-expressing beige adipose tissue. Once this tissue was in place, the scientists measured whether the mice experienced any changes in core body temperature and blood glucose levels.
The scientists reported their results August 20 in the journal Diabetes, in an article entitled, “Matrix assisted transplantation of functional beige adipose tissue.”
“While expansion of UCP1 expressing adipose depots may be achieved in rodents via genetic and pharmacological manipulations or the transplantation of brown fat depots, these methods are difficult to employ for human clinical intervention,” wrote the authors. “Subcutaneous implantation of ADMSCs within optimized hydrogels resulted in the establishment of distinct UCP1-expressing implants that successfully attracted host vasculature and persisted for several weeks. Importantly, implant recipients demonstrated elevated core body temperature during cold challenges, enhanced respiration rates, improved glucose homeostasis, and reduced weight gain demonstrating the therapeutic merit of this highly translatable approach.”
Essentially, the implant technology supported the development of beige fat, which ordinarily develops only when the body is exposed to cold, a situation that tends to stimulate increases in food intake—potentially negating any calorie-burning benefits.
“This is figuratively and literally a hot area of research right now,” said Dr. Stahl. “We are the first to implant in mice an artificial brown-fat depot and show that it has the expected effects on body temperature and beneficial effects on metabolism.”