The important question

By defining overweight as excess storage of energy in fat tissue (and consequently to little use of energy from the same tissue), we are only one simple question away from understanding what causes overweight and obesity, and ultimately how to treat and prevent it.

What factors control storage and release of energy in fat tissue?

Believe it or not, but this is actually common knowledge in physiology. Any physiology textbook will give you the answer, and the answer is even right. There are two main factors responsible for the storage of and consequently the use of energy in fat tissue. These factors are glucose and insulin, or more accurately the amount of glucose being metabolized and the level of glucose and insulin in your blood. Glucose is what most dietary carbohydrates are broken down to in your body and is what is known as blood sugar. Insulin is a very potent steroid hormone largely responsible for controlling blood sugar levels.

In order to understand how glucose controls storage and release of fat we need to understand how fat is stored. Fat is used as energy in the form of free fatty acids. These are long hydrocarbons that are broken down to create energy. When animals (humans are also animals) store energy for later use, it is mostly in the form of triacylglycerols in fat cells. Triacylglycerol is made up of three fatty acids bound to a glycerol molecule. So when the body has excess fatty acids that can be stored for later use, they are transported into the fat cell where they are bound to glycerol to form triacylglycerol (a.k.a. triglycerides). So far, so good. This all makes sense in that our fat tissue is supposed to work as an energy storage for when less food is available. Fat tissue is thus a very important evolutionary mechanism that ensures survival when food availability is not constant.

The thing is that for the body to make triacylglycerol, a molecule known as alfa-glycerolphosphate (glycerol-3-phosphate) is needed to provide the glycerol backbone of triacylglycerol. Alfa-glycerolphosphate is made in the body when carbohydrates are broken down. To put it simply, if little alfa-glycerolphosphate is made, fat tissue will lack glycerol molecules to make triacylglycerol and the fat cells cannot store energy. When the fat cells aren't storing energy, they are more likely to release energy that can be used instead of dietary energy.

But the fat tissue is not only an important energy storage, it also functions as an important regulator of blood glucose levels. Glucose is not only providing the glycerol backbone for triacylglycerols, but is also made into fatty acids. This way, the fat tissue will absorb blood sugar when or if it gets high. This function is especially important when skeletal muscles are insulin resistant and absorb little glucose. If blood sugar is dropping the fat tissue releases fatty acids for use as fuel by the cells that can metabolize fat, thus making glucose available for the cells that need this particular fuel. There are some cells in the body that depend on glucose for fuel, but the total amount needed is so small our body can make it from scratch even without getting any dietary carbohydrate.

I am talking a lot about glucose and insulin, but what about how much we eat? Doesn’t that also control how much is stored? No, it doesn’t, it’s actually the other way around. How much you consume depends on how much is stored. It’s a complicated topic, but there are two important things I’ll say now and I’ll elaborate later. Firstly, energy expenditure and energy intake are highly dependent factors. This means that messing around with one factor will cause a compensatory change in the other (more elaborate in Norwegian here:http://www.forskning.no/artikler/2009/januar/207538 and in English here: http://nymag.com/news/sports/38001/). It’s the same in all animals. Secondly, our sensation of hunger is largely regulated by the energy available for (or rather the energy metabolized by) the liver cells at any moment. The amount of energy available for these cells does not necessarily reflect the amount of energy consumed. Worst case scenario, parts of your body might be starving despite large energy stores in fat tissue. Even though we might have a lot of energy stored, it doesn’t mean this energy is available for use.

Let us sum this up. Overweight is a condition characterized by excess storage of energy in fat tissue. The main regulators of storage in and release of energy from fat tissue are glucose and insulin. Ah, we are closing in. Now we are only one question away from understanding overweight and obesity and what we can do about it. And this time it will work.