Unlike white fat that stores energy and makes your pants feel tight when you have too much of it, brown fat burns energy in the body.
Scientists don’t yet know how to activate brown fat, a potential key in preventing diabetes and obesity. However, with the recent discovery of significant pathways to brown fat activation, researchers at the Joslin Diabetes Center in Boston moved another step closer to the day when brown fat can be activated in humans with a drug or cultivated in the laboratory for transplant into humans.
“The biggest thing we’re trying to find out is how to activate this tissue to burn calories,” said Aaron Cypess, M.D., a staff physician at Joslin Diabetes Center and lead author of the study.
Brown fat was long believed to exist only in babies and children, and in animals like mice. The commonly held perception was that brown fat disappeared as humans reached puberty.
In 2004, Cypess had what he called “the perfect Eureka moment.” He was attending a lecture where the presenting physician showed slides of PET scan images of adult tissue. The physician’s offhanded mention of brown fat shown on the slides alerted Cypess. He confirmed with the presenting physician that brown fat can indeed be seen on PET scans of adult tissue, a revelation that led him to investigate its treatment potential.
“Brown fat was on my mind at the theoretical level,” he said. “But because I personally take care of patients and do clinical work along with research, I was primed to prove that it works.”
Solving the brown fat puzzle involves determining whether people with diabetes or who are obese do not have enough brown fat, or whether their brown fat does not work properly to burn energy. Cypess envisions a day when treatment will be available for obese or diabetic patients “to get their brown fat to work better.”
Right now, 25.8 million people in the U.S. have diabetes, or 8.3 percent of the population, according to the American Diabetes Association. A 2010 report by the Centers for Disease Control and Prevention issued the bleak warning that diabetes rates will rise sharply in the next 40 years, possibly reaching 33 percent if current trends continue. Knowing how brown fat works “has tremendous implications for diabetes, obesity, and human metabolism,” Cypess said.
Writing in the journal Endocrinology, the researchers described two pathways in the body that lead to a protein called necdin, which blocks brown fat growth. Researchers know now that two proteins bind directly to the necdin gene. The protein CREB inhibits necdin, and the protein Fox01 stimulates it.
The next step will be to figure out how to alter this molecular pathway. One method would be to stimulate CREB and keep necdin from blocking the growth of calorie-burning brown fat. Another possibility would be to shut down Fox01, thereby preventing this protein from ramping up necdin production.
Understanding the relationship between brown fat, necdin, and the two proteins that bind to it paves the way to design compounds or use existing medications or hormones to treat diabetes and obesity, said Cypress.
For more information on diabetes, contact the Orange County office of the American Diabetes Association. For information on diabetes education at Mission Hospital, call 949-364-1770.
