Brown fat could help fight obesity. This Penn scientist is looking to harness its power

Oct. 15, 2018

In a way, weíd all be a little better off if we had more fat, researchers are discovering.

But before you reach for the potato chips, know that theyíre talking about a different kind of fat ó brown fat, which is radically apart from the white fat that characterizes obesity. In a sense, theyíre opposites. One burns energy; the other stores it.

Patrick Seale, associate professor of cell and development biology at the University of Pennsylvaniaís Perelman School of Medicine, studies fats and their relationship to metabolic diseases such as diabetes.

Recently, the Endocrine Society, an international association focusing on hormone research, announced that he was one of 13 leading endocrinologists to get one of its annual Laureate Awards. Seale received the Richard E. Weitzman Outstanding Early Career Investigator Award for his study of brown fat.

Seale knows these issues both as a scientist and as a regular guy. ďI still struggle all the time with losing weight,Ē he said during a recent interview about his work. ďMaybe thatís why Iím fascinated with it. I just find it interesting to think about how all this works.Ē

Q: How different are brown and white fat? Are they really those colors?

A: Theyíre very different. Brown fat functions to burn energy, and it does this to make heat. The heat is really important, especially in small animals, for maintaining body temperature. For example, mice that have defective brown fat canít survive in the cold.

White fat is the most prevalent fat tissue, especially in humans. Its main function is to store energy. It expands when people eat more than they burn off.

They actually are different colors. Brown fat looks brown, and the reason is it has a lot of mitochondria ó what can be considered the energy powerhouses of the cell. They essentially make energy for cells, and brown fat has a lot of them.

The color of white fat is determined by the lipids that are stored there. Itís not really that white. In humans, itís more of a yellow tinge. In mice, itís white.

White fat is found in the subcutaneous region ó right under your skin and it surrounds your internal organs. It forms in a lot of places. Itís far and away the largest type of fat that humans have.

Brown fat ó thereís a lot less of it. And itís in very specific places. The place itís found in the largest quantities is right around the collar bone. There are also small amounts along the spinal column, and quite a bit in the neck. We donít really know why.

It might be that the collar bone, spinal column, and neck are just a good place to be for warming the blood vessels. Brown fat probably did not form to keep us from becoming obese. It probably evolved to keep us warm. The heat that it makes can quickly get to the rest of the body.

Q: So is brown fat really good for us, while white fat is not?

A: Thatís actually a little more complicated. Theyíre both good.

Brown fat is good for us because it can burn extra calories; it can expend calories that you donít want to store. You can kind of think of it a little like exercise. It will burn energy, except you donít have to work. This energy would otherwise be stored in the body, so it actually counteracts obesity in that way. Itís very clear that mice with more brown fat do very well. They are protected against obesity and diabetes.

White fat is also good. The reason is that itís essentially a safe place to store lipids. Obesity happens when more energy is taken in than is expended. That energy has to go somewhere. Up until a certain point, white fat can handle it. The energy is converted to lipid and stored in white fat. However, if the oversupply of energy is chronic, the fat cells eventually become overburdened and arenít able to store the lipid anymore. It ends up going to liver, pancreas or muscles, and that causes all kinds of problems.

Q: Can we get more brown fat by altering what we eat?

A: Not that we know of. Thereís a lot of interest in that. Large pharmaceutical companies are trying to figure out how we can make more brown fat.

The one thing people can do is to expose yourself to the cold. There are a lot of people who think that is a good thing to do.

How cold? Itís different for each person. Certainly not to the point where you shiver. There are a lot of studies now looking at reducing environmental temperature to see if that can have effects on obesity and diabetes. Itís very promising.

In one Japanese study, subjects sat in a cold room ó 66 degrees Fahrenheit ó for two hours a day over the course of six weeks. People lost quite a bit of weight.

Thereís a lot of interest in finding other ways to increase the function of brown fat.

Q: Tell us more about your research.

A: A lot of what we are trying to do is to figure out the genetic pathways for how both brown and white fat cells are made. Weíre trying to understand the molecules and all the factors that go into this, with the thought that weíll figure out how to make more of it or stimulate it in different ways for therapeutic effect.

The other thing we focus on is developing animal models so that we can understand what goes wrong in the setting of obesity and diabetes ó how that affects fat tissue, both brown and white ó and how we might be able to change the properties of that tissue to affect diabetes. When an animal or human gets obese, that has major effects on the fat tissues. So weíre trying to understand what is happening ó what is good, what is potentially bad ó so we can think about ways to intervene. If we understand the bad consequences, we might be able to block the effects. If we understand the good consequences, we might be able to promote them.

We now know a lot about how these different types of fat tissues work, and about the genetic factors that control them. Whatís needed now is to try to find ways to manipulate it, to try to find therapies that target the fat tissue, for fighting obesity as well as diabetes. In particular, brown fat holds a lot of promise for fighting obesity. Itís a tough thing to crack, but thatís probably where the main thrust of the field is ó how we can use our knowledge and develop ways to target brown fat to fight obesity. We have pretty good drugs for diabetes. Obesity is trickier. And obesity is often the thing that initiates these other problems.

Q: People tend to think fat is just bulky, but so much science is revealing that itís actually more like an organ that does all kinds of interesting things.

A: Absolutely. Even in the science community, it was previously thought of as an inert organ that is a bystander. Now, we know so much more about it. There are many different types of fat tissue. Weíve talked about brown and white. In every place in the body, the fat tissue is probably slightly different and doing different things, probably having important functions.

The other thing we know now is that, rather than being an inert organ, it makes a lot of hormones that communicate with other organs in the body. It makes things to talk to the brain, that talk to the muscles. I would say it coordinates or controls a lot of metabolism. Itís really an important thing to study.


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