This past winter, vests were a hot button issue thanks to then US presidential hopeful Rick Santorum. But a vest that cools—rather than warms—could fire up studies of brown fat as researchers seek drugs that turn on this calorie-burning tissue.
Compared with white fat, which mostly acts as an energy repository, brown fat serves to generate heat. In the past, researchers believed only babies made use of brown adipose tissue. Now we know adults have small deposits of brown fat throughout the body that burn energy only in chilly environments. With roughly two-thirds of the US classified as overweight, researchers are keen on pinpointing how brown fat is activated and how to convert white fat to its healthier cousin to help people slim down.
In February, Canadian researchers published a study in the Journal of Clinical Investigation that looked beyond brown fat’s heat-producing capabilities to how, once activated, it affects our metabolism. With a sample size of six healthy men, they reduced average skin temperature by about 4 degrees to roughly 30°C by fitting them in a cooling suit. Positron-emission tomography (PET) allowed scientists to see for the first time that cold exposure increased the amount of nonesterified fatty acids (NEFA)—the primary source of energy for tissues in fasting conditions—in the blood stream by one-third. Despite the small sample size, researchers expressed confidence in their results due to consistent measurements across the participants.
But it would be more convenient for overweight individuals to take a drug that causes brown fat to burn calories. A study published this week in the Proceedings of the National Academy of Sciences (PNAS) set out to test a possible drug therapy. Aaron Cypess of the Joslin Diabetes Center in Boston and his team wanted to determine if an ingredient found in over-the-counter decongestant drugs, called ephedrine, might activate brown fat without any cold exposure. A meta-analysis in 2003 had previously suggested that ephedrine may produce modest weight loss in humans. Ephedrine seems to cause weight loss by stimulating a release of the messenger molecule norepinephrine, thereby increasing heart rate. Brown adipose tissue has receptors for norepinephrine, so researchers reasoned the drug would activate this type of fat.
In the PNAS study, researchers tried three methods on separate visits over the course of three days. Ten participants received a single dose of ephedrine or saline solution, or were fitted with a cooling vest set to 14°C, or two degrees cooler than in the February study. Such vests are sometimes worn by surgeons in the operating room. Cypess and his team found that brown fat was reliably activated only during cold exposure, not by ephedrine.
“On the positive side, we found a way to activate brown fat in a consistent manner with cold [environmental] temperatures,” Cypess says. “Let’s say we come up with a method in the future, such as a drug, a diet. We now have a positive control [in the form of exposure to cold temperatures].” He added that cooling vests save costs compared with cranking up an air-conditioned system to lower a temperature in a room.
Cypess hopes that other methods exist to crack the mystery of what, besides cold, turns on brown fat. To that end, a report published in the current issue of Nature Medicine could offer possible clues. This study revealed that turning down the gene Aldh1a1 in mice shifted white fat tissue to be more like brown fat. Aldh1a1 produces an enzyme that converts metabolites of vitamin A—switching the molecule retinaldehyde to retinoic acid. In this month’s Nature Medicine podcast, lead author Jorge Plutzky says, “I think that someday, yes, we will have agents that allow us to manipulate adiposity. At least in the models we are studying here, it’s not a change in how much energy or how many calories are coming in, but a dissipation of energy.”
What is the next step for brown fat research? “That is the billion dollar question,” says Cypess. He explains that studies should ultimately focus on the chronic effect of brown fat activation in humans. But researchers need to proceed with caution. “It could be that we increase the brown fat percentage and find that people consume more food,” Cypess says. He envisions the next study will expose participants to cold for longer periods of time. He also gives some unsolicited advice: Don’t try this at home.
Image courtesy of PeJo via Shutterstock