Millions of people have rung in the New Year with solemn resolutions to end their addiction to fat and to rid themselves of those fat cells that bring such dark tidings of health problems to come. In the spirit of “know thy enemy” I present you with a little piece on the biology of fat.
First of all, why do we have fat? It seems like a cruel joke played by a creator intent on making us show our past weaknesses for all to see. Evolution supplies a kinder explanation. As I described in my last post, triglycerides (stored fat) are the most concentrated form of biological energy we have and fat cells are specialized tissues that store this fuel. At the time in our history when food was scarce, we needed a way to store whatever we found whenever we came across more than we could use right then and there. Fat is a sort of bank savings account for those times of famine that hunter gatherers are so used to. Those who craved fat ate more and stored more during the good times and then burned the fuel during the bad times. These were the ones who survived to breed and so we are graced with this craving – once a survival trait and now quite the opposite.
If the last paragraph completely explained fat we would be done but, as it turns out, fat does a great deal more and we are still learning about its complexities. For example, not only does fat serve as a way to store energy but it also can convert that energy directly to heat. Hibernating animals such as bears use this tissue to keep warm during the winter months. Recent data shows that we also use it also to generate heat (and given the amount of time I spend outside in the winter I probably make use of it often).
Fat which generates heat is different from fat which stores energy. It looks different as well. Fat of this type has a brown color due to pigment granules in its mitochondria while energy storage fat has the white/yellow color we see in various cuts of meats. For this reason we refer to the heat generating fat as Brown Adipose Tissue (BAT) and the energy storing fat as White Adipose Tissue (WAT). These two types of fat have very different metabolic profiles.
WAT performs a function called oxidative phosphorylation. Some of you may remember ATP from high school or college biology. ATP stands for adenosine triphosphate and those 3 phosphates store a LOT of energy. Think of a spring that is tightly compressed. The energy is stored in that compression. In the same way, high energy electrons, in the same sense, are storing that energy for later use. To generate ATP, mitochondria burn fuel in a very controlled way involving oxygen (just as fire uses oxygen). So oxidative phosphorylation is just a fancy way of saying that the mitochondria uses oxygen to burn glucose and then stores the high energy electrons that pop out as phosphate bonds in ATP.
BAT generates heat by disrupting oxidative phosphorylation. What happens in WAT is that the generation of 2 electrons is tightly coupled to the formation of the final bond of an ATP molecule. In BAT the two events are uncoupled by the presence of a protein imaginatively called uncoupling protein-1. With nowhere in particular to go, the electrons dissipate their vibrational energy as heat. I suspect some of you are wondering about shivering and how this fits into the story. When we need additional heat, our skeletal muscles are designed to begin to vibrate. This is shivering. It generates more heat to protect our core when BAT cannot handle the job.
We have a great deal more WAT than BAT. We are far too aware of where WAT concentrates; our midsections, buttocks, thighs etc. BAT is found around the neck, surrounding the large arteries, the heart, the kidneys, and the spine. Both WAT and BAT are highly adaptable and can change according to our needs. WAT expands by a process we call hypertrophy which simply means the fat cells get bigger. BAT expands by a process we call hyperplasia which means that the fat cells divide to make more of them. In general, WAT is supplied by relatively few blood vessels while the smaller BAT cells are richly supplied. This is useful as some of that vibrational energy can dissipate into the blood and warm other tissues besides those which BAT surrounds. BAT expansion occurs upon regular exposure to cold. Indeed arctic workers and deep sea divers have increased amounts of BAT. Alcoholics also have increased BAT, presumably because alcohol promotes heat loss.
WAT is the major source of triglycerides used for the generation of ATP during times of fasting. In addition, surprisingly, WAT secretes hormones that play a big role in the regulation of our metabolism as well as our behaviors regarding food. Indeed WAT is an endocrine organ. The molecules WAT secretes are many and varied. The two molecules which make the most sense are adiponectin and leptin. These protein hormones provide a certain sense of satiety. Thus one would expect, if we were actually designed, that the secretion of these hormones would stop us from eating when our bodies got too fat. Unfortunately as we are all to well aware, this does not happen. We do not really know why. If we could strengthen this connection, by designing a drug for example, we might be able to make a dent in the obesity problem that plagues our society. While disruption of the leptin gene in mice causes extreme obesity, we have not had much luck trying to use leptin as a drug. Clinical trials have been performed and leptin has proved safe – it is just not very effective. Perhaps we have not yet found the right pathway that regulates this balance. Such a pathway should exist. We certainly have no end of other WAT derived molecules to examine.
WAT also secretes hormones that cause us trouble. For example, WAT secretes inflammatory signaling molecules such as IL-6 and tumor necrosis factor (TNF). WAT also secretes angiotensin, a hormone that promotes increased blood pressure. These molecules contribute both to cardiovascular disease as well as insulin resistance.
WAT, in different regions of the body behave differently. It is primarily the WAT that surrounds our bellies (also called visceral fat) that is especially active in secreting these inflammatory signaling molecules. Another thing that visceral fat is really good at is leaking out fatty acids. These components of triglycerides cause great damage. They coat blood vessels to promote blockage (and thus heart disease). They also can serve as targets for errant electrons. These high energy particles transfer their energy to the fat molecules which then circulate and can then transfer that energy to other tissues which then become damaged. These are also known as reactive oxygen intermediates since those electrons often like to stick around oxygens. Antioxidants, to some extent, can mitigate the damage but only partially. Trans fats are particularly happy to pick up those electrons which is why we have tried to expunge them from our diets.
Going back to the question of balance, early man was quite active. One school of thought is that this activity is the missing piece that brings things together. We evolved to move but for some reason, now we don’t. Why is it that it is so hard to exercise? When a sedentary person begins exercise it can feel like torture. Only after several months of sticking with it do the benefits begin to become apparent. One would think that we would become “itchy” if we were inactive for too long a time but this does not seem to be the case. Our bodies welcome the sedentary life. Yet another question that needs answering.
A recent study published just last week in Cell shows that in fruit flies and mice we can use certain pathways like “hedgehog signaling pathways” to alter the movement of glucose into WAT but this change doesn’t effect BAT. Since BAT uses more sugars for heat generation from its thermogensis of foods, we can increase our metabolism slightly and thus burn more calories each day. Based upon my reading, we can also use a healthy diet and exercise to slowly expand BAT if you begin to lose body mass and WAT. Only a small expansion of BAT is needed to… Read more »
Fat, BAT, WAT… Is this a Rob Scheinman or a Dr. Suess post? :)
Thanks for this explanation. So interesting!