To Treat Obesity, a Bioreactor Transforms Bad Fat Into Good Fat
With an outpatient procedure, doctors could give overweight people a metabolic boost
It sounds like a medical magic trick. Obese people could have the source of their problem—the type of fat tissue that stores energy and thickens waistlines—transformed into the cure.
Here’s how the wizardry would work. An overweight person would go to a clinic for a simple procedure in which a small scrap of bad “white fat” tissue would be sucked out of his belly. Doctors would stick that piece of tissue into an automated bioreactor, where it would get a chemical bath for about three weeks.
Within that machine, it would change into the good “brown fat” tissue that helps the body burn calories to stay warm. Then the patient would return to the clinic, and the scrap of tissue would be reinserted into his body. This transmogrified tissue would raise his metabolism and help him lose weight, even without the hard work of diet and exercise.
This vision comes from the startup Ardent Cell Technologies, the brainchild of Brian Gillette, formerly a bioengineer at Columbia University and now a researcher at NYU Winthrop Hospital.
His team is developing the bioreactor that performs the legerdemain. At first, Gillette imagines that the patient’s tissue would be placed in a cartridge and shipped to Ardent headquarters, where the bioreactor would do its work. Later on, he hopes to do away with the shipping and handling. “We’re trying to develop a device that’s automated enough to be used in a clinic setting,” Gillette tells IEEE Spectrum.
Gillette says the eventual business model could resemble that of inkjet printers. “It would be a device that’s reusable, with single-use cartridges that handle each patient’s dose,” he says. “You set up the device, then you’re just ordering up these consumables for each patient.”
In a paper published on Monday in Scientific Reports, Gillette and his collaborators describe their preliminary experiments. They showed that their conversion procedure, which doesn’t require any genetic engineering, works on both mouse and human fat tissue. They also injected converted tissue into mice, and showed that the tissue retained its brown fat qualities (rather than reverting to white fat) for the eight-week duration of the study.
The researchers haven’t yet implanted converted tissue into humans, but they’re hopeful that the procedure will yield similarly durable results, with the new brown fat keeping its form for eight weeks or longer.
“Even if you have to go in and do this every couple of months, it’s not a big deal,” says Samuel Sia, one of the paper’s coauthors and a professor of biomedical engineering at Columbia University. “You could go to an outpatient clinic and keep doing this, over and over again,” he says. “It’s sustainable.”
With more than one-third of Americans qualifying as obese (and numbers rising in most other countries), there’s certainly a market for a quick and easy body hack.
Brown fat has recently become the object of intense interest to researchers working on obesity treatments. Scientists and doctors have long known that newborn babies have deposits of brown fat, and that this metabolically active tissue helps these vulnerable creatures stay warm. But brown fat deposits diminish as humans grow up, and the small bits in adults were thought to be essentially irrelevant.
A 2009 paper in the New England Journal of Medicine changed that thinking. A team led by Aaron Cypess, now head of obesity research at the National Institutes of Health, used PET scans to reveal brown fat in adults. What’s more, the researchers found that lean people had more of it than overweight people.
“The good thing about this tissue is that it doesn’t take a lot to have a big impact,” Gillette explains. An adult with ample brown fat might have 50 to 70 grams (a little more mass than that of a golf ball) distributed throughout the body. Yet “that can account for something like 20 percent of energy expenditure, which is pretty remarkable,” he says.
So the hunt is on for treatments that increase brown fat in adults—there are several ways to make white fat turn into brown fat inside the body—and thus to help them melt away their excess pounds.
Many researchers are investigating drugs that can do the trick, but most tried so far have deleterious side effects elsewhere in the body. Others are using cold exposure to make bodies generate brown fat. “There are already devices like cooling vests that you throw in your freezer, then wear around for an hour,” Gillette says. “That can work, but most people don’t want to be cold.”
Still others are trying to convert individual cells (such as stem cells or white fat cells) into brown fat cells. Ardent’s approach is different, Gillette says, because it converts a whole piece of tissue, with all the existing blood vessels and nerve cells that make it functional. And the fat grafting procedure is one that plastic surgeons already do today for cosmetic or reconstruction purposes.
But the researchers still have a ways to go to prove that their approach will really be useful to overweight people. In their preliminary experiments on mice, Gillette and Sia’s team didn’t show that the mice with the re-implanted tissue lost more weight than a control group of mice, which had equal amounts of standard white fat implanted in their bodies.
“We showed that the process works, but that’s as far as we were able to get in this study,” Sia says. He calls the results “suggestive, but not conclusive,” and says that the next round of experiments will use different amounts of converted fat in an attempt to find a “dose” that works.
Other experts are also waiting for more results. “I think the concept is really interesting, but I’d like to see more before I get too excited about it,” says Paul Cohen, an assistant professor at Rockefeller University who studies brown fat. “I look forward to future studies that further refine this technique to see whether engineered thermogenic fat can have benefits for body weight and metabolism,” he says.
Cohen adds that this engineering process might not be a killer app for weight loss. “The studies in mice and humans seem to indicate that increasing brown fat will have greater benefit on reducing blood glucose and lipids than in body weight,” he says. High levels of glucose (aka blood sugar) and lipids are two of the factors in metabolic syndrome, a cluster of conditions that increase a person’s risk of developing diabetes and heart disease.
Gillette and Sia both say their technique might end up being complimentary to other weight-control approaches, such as bariatric surgery or a lifestyle change that involves diet and exercise.
“Most of those other approaches restrict energy intake,” Gillette says. “This works on the other half of the energy equation.”