A newly identified signaling pathway that stimulates glucose uptake in brown fat cells could have game-changing implications for the treatment of type 2 diabetes and obesity. The new research, published in The Journal of Cell Biology, suggests that brown fat acts as a “super-vacuum” and can actually draw glucose cells from the blood, helping the body regulate blood sugar levels while also burning off extra energy.
Brown adipose tissue, or brown fat, is a specialized tissue that burns calories to generate body heat in rodents and newborn humans, neither of which shiver. Recently, adult humans have also been found to possess brown fat. This fact piqued the interest of researchers seeking to combat the obesity epidemic, the thought being that they could induce weight loss if they could develop ways to increase the amount of brown fat a person has.
Unlike white fat cells, which store the body’s surplus energy in the form of fat, brown fat cells have the unique property of being able to burn energy and turn it into heat. When the body encounters cold temperatures, the sympathetic nervous system activates adrenoceptors on the surface of brown fat cells to stimulate glucose (sugar) uptake from the bloodstream. Brown fat cells then use this glucose as a fuel source to generate body heat.
Glucose uptake also can be induced by insulin. However, although insulin-stimulated glucose-uptake is well understood, the mechanisms involved in the adrenoceptor-dependent process have been unclear.
Now, researchers in Sweden have revealed a key piece of the puzzle, finding that the mTORC2 signaling pathway is the key regulator of adrenoreceptor-stimulated glucose uptake in brown fat tissue in mice. The pathway, which involves a protein kinase called mTOR, stimulates the transport of a glucose-importing protein called GLUT1 to the surface of brown fat cells.
In other words, brown fat can actually “vacuum” glucose molecules from the blood by producing large amounts of GLUT1, which transports glucose into the brown fat cells where it can be burned to produce heat — a process called thermogenesis. Brown fat cells do this at a more efficient rate than other mechanisms the body uses to absorb glucose in the blood: When activated, the cells produce 10 or more times the amount of glucose transporters than insulin, the researchers said.
For people with type 2 diabetes, whose bodies do not use insulin properly and as a result have elevated blood glucose levels, these findings could lead to new drugs that can activate brown cells and reduce blood glucose levels without insulin.
“One of the most interesting characteristics of this newly discovered signal pathway is that it differs from the signal pathway triggered by insulin,” says senior author Dr. Tore Bengtsson from the Department of Molecular Biosciences, Wenner-Gren Institute, Stockholm University. “This means that the signal pathway in brown fat can most likely be activated even in patients with type 2 diabetes, where insulin signaling is impaired.”
In addition to being an effective tool for controlling blood sugar levels in type 2 diabetes patients, these findings suggest that stimulating the mTORC2 pathway to take advantage of the energy-burning power of brown fat might be effective as a weight loss therapy.