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Drug Activates Brown Fat and Increases Metabolism

Humans have several types of fat. White fat stores extra energy. Too much white fat, a characteristic of obesity, increases the risk of several diseases. Brown fat (also called brown adipose tissue), in contrast, burns chemical energy to create heat and help maintain body temperature. Since brown fat burns energy, boosting its activity could potentially aid in the treatment of metabolic conditions, such as type 2 diabetes.

Brown fat cells have β3-adrenergic receptors on their surface. These protein receptors span the cell membrane and serve as gatekeepers to transmit signals between the outside and inside of cells. Several other tissues also have β3-adrenergic receptors, including white fat and the bladder. A new drug called mirabegron activates these receptors and has been approved by the U.S. Food and Drug Administration to treat overactive bladder.

Dr. Aaron Cypess—now at NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), while working at the Joslin Diabetes Center in Boston—and colleagues examined whether this drug might activate β3-adrenergic receptors on brown fat cells to increase metabolism in humans. The research was supported in part by NIDDK and by NIH’s National Center for Research Resources (NCRR) and National Center for Advancing Translational Sciences (NCATS). Results were published on January 6, 2015, in Cell Metabolism.

The team screened 15 healthy, lean men for participation in the study. Of these, 12 showed detectable levels of brown fat. These men, average age 22 years, underwent 2 additional imaging tests on 2 different days. For one test, each took a single 200 milligram dose of mirabegron. For the other test, each received a placebo.

Several hours after taking the drug or placebo, participants received infusions of a traceable form of glucose. The researchers found that participants had increased glucose uptake in several tissues, including brown fat, after taking the drug mirabegron. Using PET and CT scanning, the scientists found that the drug increased brown fat metabolic activity. Resting metabolic rate also rose by an average of 203 calories per day. The increase in metabolic rate was associated with the increase in brown fat activity.

The researchers found that the drug caused an increase in resting heart rate and systolic blood pressure in the men, which are signs of cardiovascular system stimulation. The drug also stimulated white fat.

“Brown adipose tissue, or brown fat, produces β3-adrenergic receptor at levels higher than nearly every other organ in the body. We showed that a one-time dose of the drug mirabegron stimulates human brown adipose tissue so that it consumes glucose and burns calories,” Cypess says.

The team notes that since this was a small study conducted in healthy men, and the men only took the drug 1 time, much more research will be needed to determine the safety and feasibility of activating this pathway as a way to increase energy expenditure.

—by Carol Torgan, Ph.D.




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