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Counterintuitive Cure? Researchers Aim to Reduce Obesity—With Fat Implants

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Posted November 10, 2015

We’ve tried countless ways to cure our national obesity epidemic—from the First Lady’s “Let’s Move” evangelism to invasive bariatric surgery. The latest potential strategy to help people lose excess weight: fat implants.

It may seem like a paradox, but it hinges on the kind of fat we’re talking about. Only one type of fat in our bodies makes us overweight—white fat, which stores energy. The other, called brown fat, burns fatty acids and glucose and releases that energy as heat. Having more brown fat means your basal metabolic rate (the rate of burning energy when doing no physical activity) shoots up. Infants, who can’t shiver, have an abundance of brown fat. As we get older and our muscles allow us to shiver, the brown fat in our bodies declines, and white fat plays a larger role.

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While this is great news for a civilization that once struggled to preserve energy, calories are now so readily available that much of our white fat is excessive, performing its duties too efficiently.

Since brown fat was recently discovered to still exist in small quantities in the adult human body, researchers have been intrigued by the tantalizing question of how to increase brown fat in adults, particularly those with metabolic disorders such as obesity and Type II diabetes. One known method of increasing brown fat activity: prolonged exposure to significant cold. But for people who don’t care to permanently relocate to Alaska, a team of UC Berkeley researchers is experimenting with a way to make white fat act like brown fat. They have dubbed this new version “beige fat.”

Researchers Kevin Tharp, a Ph.D. student in the department of nutritional sciences and toxicology, and Amit Jha, a postdoctoral researcher, are aiming to turn energy-storing fat into energy-burning fat with a minimally invasive procedure. With advice and support from Andreas Stahl, an associate professor of nutritional sciences and toxicology, and Kevin Healy, professor of bioengineering and materials science, they report successfully developing a beige fat implant that’s working in mice. More brown (or beige) fat means less fatty acids, lower blood glucose levels, decreased inflammation of the liver, and more body heat.

As Tharp says: “It’s out with the bad and in with the better.”

The team created the implant by performing a sort of liposuction of white fat from a mouse, extracting its stem cells so that the fat is no longer coded to behave like white fat, and then injecting it into a hydrogel created by Jha. The gel contains protein sequences associated with brown-fat growth and function, thus providing growth cues that make the stem cells act like beige fat. As Tharp explains, “If you can get fat stem cells from your body into the hydrogel, they’ll become beige fat.”

Then researchers took this new creation—wrapped in the gel scaffold to keep it from being attacked as a foreign substance in the body—and implanted it under the skin, into the fat pad in the groin region of the mouse. Mice with the implant gained half as much weight and maintained lower levels of blood glucose and fatty acids when placed on the same high-fat diet as the control group. The mice with implants also demonstrated up to half a degree Celsius higher core body temperature than the control group.

The implant is completely separate from affecting any other cellular system in the body, thus avoiding some negative side effects that other treatments might induce. The hydrogel uses physical instead of bio-chemical cues that many pharmaceutical treatments employ. Tharp describes it as “ biochemical braille.”

Tharp and Jha say they believe the therapy is very likely to work in humans, but acknowledge that the implant still requires work. In its current state, Tharp says, it would be more expensive than beneficial. They want to find ways to encourage even more elevated activation of beige fat with their implant, as well as create a simpler way of installing, and eventually removing, the implant itself. The goal: to create a one-step process in which the metabolic therapy lasts longer and has more powerful effects.

The team is now working on a concept where no stem cells would be required in the implant, thus making the procedure simpler and less expensive. They wish to create something that recruits cells from adjacent fat “depots”—areas in the body where large quantities of fat are stored—and converts the fat depot into beige fat cells. This would theoretically be done by injecting a hydrogel into or next to a white fat depot.

This research, funded in part by the National Institutes of Health and the American Diabetes Association, may indeed lead to a productive therapy for obesity and diabetes—both by helping take fatty acids and glucose out of the system, and relieving inflammation in the body. However, as with all “easy fixes,” there is a catch: While the implant is in, and especially once it is removed, patients will need to maintain a healthy lifestyle to experience benefits. Yeah, we still haven’t found a way to cheat exercise and a healthy diet. But, until then, it would be nice to get an FDA-approved metabolism boost.

Source: UC Berkeley

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