Deep within your body, there are two forces at work. One is on the side of light and most everyone is aware of its presence. But there’s another, lesser known side to the same coin. Few people know of its existence; even scientists weren’t aware that it resided in humans until relatively recently.
It’s the dark side.
And you should embrace this dark side. It’s here to help you. Rather than shutting it out, in fact, scientists are trying to figure out how to make even more of it and keep it from shutting down in the bodies of the people of the world.
I am talking, of course, about fat. Pretty much everybody is all too aware of the white, flabby stuff that sticks out of terrible, terrible crevices of people who wear too tight of clothing. The website www.peopleofwalmart.com should be a sufficient lesson on the ills of not owning a mirror or any self-respect.
However, there’s also a darker kind known as brown fat that serves a much different purpose. Rather than storing energy – which is, after all, the role of the regular jelly roll variety – it burns energy in order to regulate body temperature. For instance, mammals that hibernate use brown fat to keep their bodies warm during the winter months. Mice have a decent amount, which keeps them warm in cool temperatures. And it’s been known for a while that human infants also have a lot of brown fat in order to keep them nice and cozy. Because, in case you didn’t know, babies don’t shiver.
But until recently, scientists thought all of a baby’s brown fat disappeared as it grew. As it turns out, most of us have a little bit left lining our skeleton and skeletal muscles. And just like brown fat in babies and mice, our adult brown fat burns calories instead of storing them. It may come as no surprise then to learn that slender people tend to have much higher amounts of brown fat than gigantic blimp people.
So what I’m naturally saying is that you should totally buy this book on how to exercise in order to ramp up your stores of brown fat! All you have to do is the right kinds of exercises and eat the right kinds of food and your body will make a ton of the calorie-burning brown blessing! If you don’t believe me, believe the book’s author, a plastic surgeon from Connecticut. Who else would know how to make and activate a complex biological componenet that continues to stump the best minds in the biomolecular fields?
Yes, I’m being facetious. As you might guess, the body is much more complicated than that, and it takes just a tad more than eating and moving in certain ways to get it to behave in a new, slightly unnatural way on a cellular level.
There is a lot of work being done at this very moment on how to get more brown fat in the bodies of your average person. Some studies are trying to identify molecular switches that determine whether developing fat cells become white or brown. Others are trying to identify gene regulators that can direct muscle cells early in development to differentiate into brown fat instead of muscle fiber. And while both studies have identified markers that seem to have some effect on the production of brown fat, both have only been done in mice and neither is anywhere close to developing the entire picture.
Let’s suspend reality for a second and suppose that science could make the human body produce higher levels of brown fat. Most of the time it does little more than sit around; it only gets activated when animals go into hibernation or get really cold. How many of us would want to move to Michigan’s Upper Peninsula in order to drop a few pounds?
Thus, there’s a second branch of research on brown fat dealing with how to turn on the brown fat that some of us already have. That’s where today’s featured publication comes in. Slowly but surely, researchers are identifying the molecular pathways that lead to brown fat’s energy consumption getting flipped to the “on” position.
There are several sure signs that brown fat has started burning the midnight fat, including an increase in the breakdown of the body’s lipids, an increased uptake of circulating sugar, and an increase in the activation of a protein called UCP1. That last one, in fact, is found only in brown fat, making it a great target for molecular biologists.
All of these processes are controlled by what’s called a “second messenger.” It is within a cell’s best interests to keep most everything that is outside of itself, well, outside of itself. Even the body’s own messengers are shut out. When hormones get released, they don’t actually ever get inside of a cell. Instead, they interact with receptors on the cell’s surface and second messengers relay the signal to the proper structures within the cell.
So it’s the job of these second messengers – specifically cAMP in this case – to tell the brown fat’s “batteries” (mitochondria) to start their engines and begin burning fuel. But the chain of command doesn’t end there. There’s a whole other class of molecules that regulate the cAMP called cyclic nucleotide phosphodiesterases, or PDEs for short.
I know. That’s a bunch of big, scary words. But they’re really not so bad. A phosphodiesterase is an enzyme that breaks apart phosphodiester bonds – the backbone of the helical strands of DNA and RNA.
In short, different types of PDEs destroy different types of DNA and RNA, and the cyclic nucleotide type has an appetite for the RNA of cAMP.
In shorter, PDEs destroy cAMP, which turns on brown fat.
A recent study from the University of Washington took a look at several types of PDEs to see which ones might play a role in signaling cAMP to turn on the calorie burning duties of brown fat. You could look at it as any good Italian mobster family would. If you want a person bumped off, you go to the guy who regulates the goons, a certain Don Corleone.
But if you’re smart, you won’t go straight to the horse’s mouth. Instead, you’ll get his wife Carmela to play some devil woman mind games to get him to tell the goons to snuff out your target. You’ll go to the regulator of the regulator of the killers. And coming full circle, the researchers at the University of Washington went to the regulator of the regulator of brown fat.
The study showed that no single type of PDE was responsible for getting the brown fat turned on; it requires a combination of several actors. More specifically for all you biochemists out there, it took a combination of PDE3 and PDE4 to stimulate glucose uptake in the brown fat of warm but starving mice.
And the condition of the mice was key. If they were cold, the brown fat would be turned on anyways. Keeping them above 86 degrees Fahrenheit took away any background noise that would muddle up the results, which turned out to be interesting.
It seems that it’s not the production or presence of the cAMP regulators that is important in the activation of brown fat; those molecules seem to constantly make brown fat fairly active no matter what. It’s the PDEs that chew up all of the cAMP that keeps brown fat deactivated.
In the words of first author, Steve Kraynik, “What is most interesting about our work is that brown fat seems fairly active at all times, but it is the PDEs that keep it in a subdued state. That’s why taking out the PDEs appears to turn the brown fat on. Certain receptors cause the cells to have cAMP being made all the time, but the PDEs may be working to chew it all up.”
P.S. – You may be wondering why I’m covering the University of Washington on a Big Ten science blog. The first author of the study went to Ohio State, so I think that’s enough to count. And like a lot of research papers out there, this one was responsible for getting a graduate student a Ph.D.
The paper, “PDE3 and PDE4 isozyme selective inhibitors are both required for synergistic activation of brown adipose tissue,” was published in Molecular Pharmacology by Steven Kraynik, Robert Miyaoka, and Joseph Beavo of the University of Washington.