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Q&A: When Bad Fat Goes Good

Philip Kern, MD, professor at the University of Kentucky and director of the Barnstable Brown Diabetes and Obesity Center
Philip Kern, MD, professor at the University of Kentucky and director of the Barnstable Brown Diabetes and Obesity Center

Endocrine News talks to Philip Kern, MD, at the University of Kentucky about the phenomenon of “beige” fat and what it means for the future of obesity research.

Heat usually melts fat — like butter in a sunbeam — but in mammals, cold may actually burn off adipose tissue. For “brown fat,” this is no surprise. Brown fat exists mostly in infants and mammals that live in low-temperature environments, working as an efficient heat source for the body. Unfortunately, adult humans are generally covered in “white fat,” which until now was thought to be of little use aside from a cushion.

Philip Kern, MD, professor at the University of Kentucky and director of the Barnstable Brown Diabetes and Obesity Center, discovered that white fat can turn “beige” when exposed to cold. Interestingly, obese subjects demonstrated far less “beiging” in their adipose samples than subjects at a healthy weight.

Kern spoke to Endocrine News about his findings and described the techniques used in fat-testing experiments.

Endocrine News: What are the main differences between white, beige, and brown fats?

 

Phillip Kern: All mammals have the ability to fight off cold exposure to varying degrees. When a bear is storing up fat for the winter, a lot of that is brown fat because it has to generate heat to stay warm in its cave. Brown fat has a lot of mitochondria, which normally generate ATP, but “uncoupling protein” allows the mitochondria to dissipate the energy in the fat and provide warmth.

Humans evolved to survive as hunter-gatherers. A newborn baby has to be able to stay warm, so babies have substantial amounts of brown fat located around the neck and between the scapula and central back. This has been known for a long time.

In addition to brown fat, we discovered that our white fat has the ability to not become brown exactly, but become something in-between. That’s why it’s called beige.

The subcutaneous white fat that surrounds our bodies actually can turn on some of the same genes that are found in brown fat. When it does, it causes our white fat to also dissipate energy as heat. It doesn’t become as active as the brown fat. Brown fat is like a thermogenic machine.

Adults have some brown fat, but not much — maybe 10 or 15 grams — whereas we probably have 20 – 50 kilos or more of white fat. So if we can turn on our thermogenic machinery in our white fat, even to a small extent, it could potentially be very significant in terms of burning up calories.

EN: What other methods are used to test this cold exposure process?

PK: If I were to take an average adult right now and do a PET-CT scan, which is a clinical scan that will identify brown fat, chances are that I would not find any. However, if I then chilled this person, which has been done in a variety of ways, and repeated the PET-CT scan, some of the brown fat would probably come out. To chill the core body, researchers have performed experiments where they wrap participants in a vest and circulate ice water through it.

What I did, firstly, was take fat biopsies from regular people in the summer versus the winter — just abdominal subcutaneous fat. And I found that the genes involved in beiging, that cause thermogenesis, were about fourfold higher in the winter.

The increase in these thermogenic genes was not present or was minimally present in obese subjects, suggesting that as people become obese, they may lose this ability to beige.

We also gathered some volunteers and took a fat biopsy on the anterior thigh on one leg. Then we put an ice pack on the other leg and took a biopsy four hours after. We saw the same thing. An acute exposure [to cold] caused an increase in the beiging genes.

EN: Can beige fat turn back into white fat after the cold exposure passes?

PK:Yes. First of all, we need to know a lot more about this, but we believe that our white fat cells have certain plasticity to them. If there is a stimulus, like cold exposure, then many of these white fat cells can become beige. But if cold exposure passes, they can then go back to white again. So it is really a bidirectional pathway depending on the stimulus.

EN: What are the next stages of research?

PK: I want to better understand the role of the immune system in this process. I mentioned that obese subjects do not seem to beige up their white fat as well. I think one of the reasons is because obese subjects tend to have more inflammation — including inflammation in their fat tissue. I think that there’s an inhibitory effect of this chronic inflammation on the beiging process.

There is evidence in the literature that the immune system is important in beiging. Now, most of this has been done in mice, but there is a suggestion that a cold stimulus seems to trigger a variety of inflammatory cytokines, which actually stimulate the beiging process.

So you have this conundrum. On the one hand, you have this evidence that inflammation inhibits beiging, but then on the other hand you have evidence from a different angle that suggests it is an important part of it.

It probably depends on what kind of inflammation. Inflammation can be bad, or it can actually be part of a natural process. I think that is the key thing to try to figure out right now.

— Mapes is a Washington, D.C–based freelance writer and a regular contributor to Endocrine News. She wrote about the artificial pancreas in pediatric patients in the May issue.

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