A Brown Fat Story

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Brown fat active in adult humans

What if you could burn off pounds by just chilling out? A certain type of fat may, in effect, let you do just that. Researchers at Joslin Diabetes Center and elsewhere have been looking into these types of cells that activate in the cold, called brown fat, since the discovery of its activity in human adults in 2009.

Prior to this breakthrough, brown fat had only been confirmed in babies and growing kids. Unlike most cells, which store converted food energy as the much-maligned white fat, brown fat turns that energy directly into heat. A number of studies since 2009 show that half to two thirds of adult humans have a form of this heat-producing fat, mostly stored around their necks, that gets activated when body temperatures start to decrease.

Finding Fat

In the 1970s and early 80s, researchers were hot on the brown fat trail. They knew it existed between the shoulder blades of animals, and they thought the same might be true of humans. But as searches and scans came up empty, researchers’ enthusiasm waned.

Some people kept looking, including then-medical student Aaron Cypess, M.D., Ph.D., Investigator in the Section on Integrative Physiology & Metabolism, who gave a particularly memorable talk in to a group of skeptical researchers.

Dr. Cypess suggested that some unidentified stuff sitting along the collarbone and around the neck of adult humans might have been the very thing people had been searching for.  “I showed [scans] at a talk and said ‘maybe there’s brown fat there!’” said Dr. Cypess. A researcher in attendance got in touch with him, “and he said ‘no.’ I have the emails,” Dr. Cypess continued.

Three years later, Dr. Cypess, along with a team of researchers at Joslin, announced that not only was that stuff brown fat, it was active.

Why All the Excitement?

Simply put, brown fat burns calories.

And that’s different from white fat. You eat food. That food gets broken down in your body, and its constituent molecules are used as fuel within your body’s cells. That food energy fuel usually gets converted in your cells into a thing called ATP, which is used almost like a power source for the cell. But if the cells make too much fuel for the cells to use at any given time, they store the leftover as unhealthy white fat.

Dr. Aaron Cypess

Brown fat takes the energy from food and turns it directly into heat—no ATP middleman, so nothing that needs to be stored. It’s just direct calorie burn.

“The analogy would be this: let’s say you’re driving a car, and you’ve shifted into neutral and you rev the engine. You’re not going anywhere, but you’re consuming fuel,” said Dr. Cypess.

Some people with a lot of brown fat actually radiate heat. Dr. Cypess’ has run some human experiments in which he cools the study subjects down using a vest filled with chilled water in attempts to activate and study the brown fat. “The ones who have a lot of brown fat, when we put the cooling vest on them, …they tend to heat up the water. And we have to keep making sure that the water temperature in the vest is at the target temperature,” said Dr. Cypess.

Is IL-6 the Key?

Calorie burn is not the only benefit. It seems brown fat can help the whole metabolic system.

In December 2012, Joslin researchers Kristin Stanford, Ph.D., and Laurie Goodyear, Ph.D., both in the section on Integrative Physiology & Metabolism, conducted a study in which they transplanted active brown fat into mice fed either a normal or a high fat diet. Both groups showed improvements in glucose tolerance, insulin sensitivity, body weight and fat mass. Three control groups showed no such improvements.

Dr. Kristin Stanford

One of the things researchers noticed during this study was an increase of a hormone called IL-6 in the subjects with  the brown fat transplant. This hormone had previously been linked to improved metabolism.

“When we transplanted brown adipose tissue that produced IL-6, we saw an improved metabolic effect,” said Dr. Stanford. “When we transplanted brown adipose tissue that was deficient in IL-6, we did not see the same effects. So this really suggests that the IL-6 was essential in terms of metabolic improvement, and that it was IL-6 from the brown adipose tissue.”

It’s all about Working Together

So, white fat is bad, and brown fat is good, right? Well, as with most things, the story is more complicated than black and white—or, in this case, brown and white. It turns out that white fat supplements the actions of brown fat by having the ability to “brown” itself.

So far, the process behind browning remains unclear. Some theories say that white fat cells can turn directly into brown fat when stimulated properly, either through experiencing cold or interactions with different proteins and hormones.

Another suggests that the precursors to fat still exist within white fat cells.

Before white fat cells became white fat cells, they were in a precursor state. In that state, they had the potential to become either brown fat or white fat. Their environment dictated that they grow up to be white fat, but the brown fat potential might still exist within leftover precursor cells tucked away somewhere in the white fat. When those white fat cells encounter certain proteins or hormones in the body, the precursor cells could re-activate and start making the white fat act like brown.

Dr. Yu-Hua Tseng

Experiments have shown that having these two types of fat could help in situations where one type is lacking. Yu Hua Tseng, Ph.D., Investigator in the section on Integrative Physiology & Metabolism, altered certain receptors in mice, resulting in the study subjects being born with impaired brown fat. She assumed that reduced brown fat activity would be a detriment to energy balance, leading to fewer calories burned. She fed the subjects a high fat diet, expecting them to become obese when the benefits of brown fat were removed.

“But it actually turned out to be a big surprise, these mice were able to maintain body temperature, and when we put them on high fat diet, they also don’t become more obese,” she said. “And it actually turned out to be that these mice developed more, a lot more, of those [beige fat cells] in white adipose tissue.” This means that the beige fat stepped in to get the job done when it sensed the brown fat was lacking.

Beige fat could be a key to leanness

And there might be more to having different types of brown fat than simply back-up players. Some experiments suggest the more “beige fat” (that is, white fat that has been “browned”) subjects have tucked between their muscles, the leaner they are.

In a study published 2007, researchers led by C. Ronald Kahn, M.D., co-head of the Section on Integrative Physiology & Metabolism, showed that when mice with lots of beige fat were fed a high fat diet, they were resistant to obesity. They could eat as much as they wanted, but they wouldn’t put on weight. The controls that didn’t have excess beige fat were easily susceptible to weight gain from overeating.

“[This finding] makes it really appealing that if we have more of these cells maybe it’s going to help us fight obesity,” said Dr. Tseng.

The Brown Fat Turn-On

Brown fat isn’t always active. For these beneficial effects to happen, the fat needs to be turned on.

“The way that brown fat is activated in the body normally is that you sense cold, the brain says ‘I’m cold!’ and sends out a message through the sympathetic nervous system, the same as the fight or flight concept,” said Dr. Cypess. This fight or flight system releases a hormone known as norepinephrine.

Brown fat cells

This hormone binds to many different kinds of receptors, and each receptor performs a different bodily function in the fight or flight response. One receptor increases heart rate, and  one causes blood vessels to dilate. One—the one that brown fat researchers are interested in—is located on smooth muscle and fat. It prompts the brown fat to start burning calories.

This receptor has been the focus of many investigations hoping to create a drug to turn on brown fat.  But there’s a catch.  Researchers need to figure out a way to stimulate only that brown fat receptor — without inducing a spike in heart rate and blood pressure that activating all the receptors would cause. So far, experiments have been successful in animals with a doubling of brown fat mass in 10 days.

“So there’s been a real interest …in finding [such a drug] that works in humans,” said Dr. Cypess.

Other very recent studies suggest that certain proteins and hormones in the body can also turn the calorie burning and metabolic improvement function on.

Looking to the Future

This research into brown fat activation has opened up a whole new world of potential for type 2 diabetes and obesity treatment. Many pharmaceutical companies are interested in taking these proteins and hormones and developing medications that can activate the brown fat. This type of drug couldn’t replace the benefits of regular exercise, but it could certainly help jump-start a weight loss program.

Another potential for brown fat treatment borrows from a branch of research into iPS cells.

iPS cells are stem cells, meaning they have the potential to become anything in the body. But unlike embryonic stem cells, iPS cells are derived from adult humans—say, skin cells taken  from the hand of a patient who needs treatment with brown fat therapy.

Those skin cells can be forced into the stem cell state in a lab, and then made to become brown fat. That brown fat could then be transplanted into the patient, where it can rev up the metabolism and burn calories for heat.

“We know obesity causes so many other metabolic disorders, metabolic syndrome, diabetes, cardiovascular disease, and a lot of individuals are almost genetically predisposed to obesity so it’s really hard for them to lose weight just by exercises or through diet,” said Dr. Tseng. “Currently, the most effective way to help these individuals to lose weight is bariatric surgery.” This is effective, she says, but not trivial. She hopes creation of brown fat treatments, be they drugs or transplants, can help ease some of the burden for these people struggling with obesity.

“I think it’s actually a pretty practical treatment, or approach,“ she said. “I don’t think it’s a science fiction now.”

6 Responses to A Brown Fat Story

  1. Very interesting since at times my body feels very warm The feeling seems to come between my shoulders. I am not obese but would like to reduce my weight
    I am 5 ft 1 . Believe my metabolism is slow because of thyroid medication

  2. Rich Alessi says:

    This brown fat treatment seems very promising for obese type 2 diabetics.. Please keep up the good work.
    Ra

  3. J.P. (Hans) Stock says:

    Read your blogs regularly and with interest as I’m type 2 diabetes patient. I would very much appreciate to be kept informed when treatment with brown fat becomes a realistic possibility. If a had the funds available I would come over for such treatment, but unfortunately I don’t …
    Do you know of similar research in or near the Netherlands ??
    Thanks and keep up the good work !!
    Best regards,
    Hans Stock
    The Hague
    The Netherlands

    • Aaron Cypess says:

      Hello Mr. Stock. The Netherlands has produced some of the most important work on human brown fat. One group is led by Wouter van Marken Lichtenbelt in Maastricht, but a recent paper on ethnic origin and brown fat activity came from Academic Medical Center in Amsterdam.
      Aaron Cypess, MD, PhD

  4. Lynn Yost says:

    I’d like to be on your mailing list also. I have CIPN (chemo-induced peripheral neuropathy) and all my metabolic functions are depressed (pre-diabetes, I recently lost my gallbladder, and I get cold if I don’t get enough fat in my diet). This could be a helpful adjunct therapy. Lynn in PA

    • Hi Lynn,
      You can subscribe to get our eNews right on this page. Just fill in your email address where it says subscribe (it’s just under the “Give Now” button at the top right of the page). Comment back if you have any trouble getting registered.

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