I once wrote a short paper about menstrual disturbances in female athletes. Menstrual disorders seem to be more prevalent in athletes than sedentary controls and more prevalent in sports emphasizing leanness. Elite athletes also have higher menarche age compared to non elite athlete controls. Menstrual disorders increase the risk of low bone mineral density, stress fractures and infertility. One hypothesis put forth to explain the apparent increased risk of menstrual disturbances was “the body fat hypothesis.”
The body fat hypothesis originates from observations showing that females with extremely low body fat where amenorrheic (absence of menstrual cycles for more than 90 d) and that amenorrheic athletes had lower body fat percentages than eumenorrheic (normal menstrual cycles) athletes. But, when simply matching eumenorrheic and amenorrheic athletes for body fat, it was found that the body fat hypothesis could not explain the prevalence of menstrual dysfunction in athletes. Amenorrhea often occurs in the general adolescent female population, even in the absence of substantial undernutrition or underweight, and there are many underweight and lean athletes who still maintain their menstrual function.
Sudden strenuous exercise induces amenorrhea in humans and more so if the exercise is compounded by weight loss. This caused scientists to speculate if a negative energy balance is a causal factor in menstrual disturbances. It was in researching this I stumbled over the work of George Wade, and he really opened my eyes. Starving an animal will cause it to lose its reproductive function. The simple explanation of why an energy deficit causes disruption of the reproductive function is that reproductive function has a low priority in the survival of mammals. Functions essential for survival are those of basic cellular maintenance, keeping correct body temperature and locomotion to obtain food. These functions are maintained at the expense of other functions (e.g. reproduction, storage of energy as fat and growth).
Wade et al. points out that;” …it is worth noting that the low priorities of both reproduction and fat storage vis-a-vis processes necessary for survival could account for their habitual association. Exercise, exposure to low temperatures, excessive fat storage, or poorly controlled diabetes mellitus illustrate this second point.”
When energy balance is discussed, it is implicit that we are discussing the whole body. But the theory of energy balance is inaccurate when simply defined as “energy intake minus energy expenditure.” It is inaccurate simply because the energy availability of the whole body does not necessarily reflect the energy availability of specific cells (e.g. the ovarian cells). So the important question is not necessarily if the body is in a negative energy balance, but rather what factors may cause a local energy deficit independent of total energy balance?
In a study by Tomten and Høstmark, 20 long distance runners were compared. 10 of the athletes had regular menses (control) and the other 10 athletes reported irregular menses. In the latter group a statistically significant negative energy balance was found. But the energy deficit was primarily because of a lower intake of dietary fat. Tomten and Høstmark conclude; “Present results might indicate that a high CHO/low fat diet could promote an inadequate EI (Energy Intake; my explanation) in recreational or sub-elite athletes and could cause energy deficit and endocrine disturbances.”
Although a restriction in dietary fat intake is often found in athletes, it is not often referred to as an independent hypothesis. This might seem odd, given that there do exist a perfectly reasonable physiologic explanation for the link between dietary fat and menstrual disorders.
A diet comprising of mostly carbohydrates is more likely to give higher insulin load than diets with more fat and protein.
Injected insulin disrupts reproductive function in animals. In the words of Wade et al. “When food intake is limited or when an inordinate fraction of the available energy is diverted to other uses such as exercise or fattening [my bold], reproductive attempts are suspended in favor of processes necessary for individual survival”. In animal studies, feeding a high-fat diet may ameliorate reproductive deficits. Energy deficits resulting from inadequate energy intake are also more extreme when consuming a high carbohydrate diet.
Obese women also seem predisposed of menstrual disturbances. Many women get pregnant only after loosing weight. This may seem counterintuitive. Wouldn’t nature prefer a mother with large energy stores and thus a grater chance of caring for her young through hard times? Well, as it seems, nature would prefer a certain amount of extra available energy, as illustrated by the loss of menses with extreme leanness. But, in the case of overweight and obesity we are fooled by an apparent surplus of energy. To be more precise, the fat cells have a surplus of energy, but that tells us nothing of the energy available for other tissues. The menstrual disturbances in athletes are in part likely caused by low energy availability for the ovarian cells, and when we are talking reproduction, these are the cells that count.
Yet another indication that a local starvation may exist is a finding that myostatin secretion is may be close to 3 times higher in insulin resistant obese subjects than in lean controls. Myostatin is a natural regulator of muscle tissue growth. Removing myostatin will make you look like a human version of the Belgian blue (just type myostatin in Google). Increased myostatin secretion is seen with fasting, hunger and very low energy intakes. This might be an important evolutionary adaptation by which our body breaks down superfluous muscle protein for glucose production.
When muscles are insulin resistant, they cannot take up sufficient glucose. In addition a high insulin level may make stored fat unavailable. So from the muscles point of view the body is starving independent of the amount of stored energy in the body. For an overweight insulin resistant person this may become a downward spiral with a gradual decreased ratio of muscle mass to fat mass.
Insulin resistance and polycystic ovarian syndrome are commonly associated. PCOS is a condition characterized by excessive cyst growth on the ovaries and will often cause infertility. Funny thing is that this condition is best improved by carbohydrate restriction. One explanation is an improved energy flow to the ovaries.
As a final closing argument several studies of carbohydrate restriction have reported muscle growth without increases in exercise level. It is as if the muscles are finally given the energy they need to respond and grow to mechanic stimuli.
Much has been said about hunger. The sensation is often considered largely under cognitive control. An overweight person seeking counselling is asked to eat less, despite claiming to already be hungry most of the time. Hunger is in this case simply considered by the treating authority to be suppressed by a strong will of mind. Sadly, it doesn’t work that way.
Many theories have however been presented in an attempt to explain hunger through physiological processes. Amongst these are hunger and satiety centres, the glucostat and lipostat theory and body weight set point. Unfortunately most of these fail to explain the observations in a satisfactory way. There is however a less known hypothesis which manages to explain most observations quite well. The consequence of this hypothesis however, is that macronutrient intake may play a very important role. Not because they contain different amounts of energy, but because they influence our metabolism in different ways.
Hunger might seem easily understood, as we get hungry when we don’t eat and feel sated when we do. But this is a gross oversimplification. If we fast, we may feel extreme hunger during the first day or two, but then as ketone body production sets in and fat metabolism is up regulated, hunger is diminished despite the complete lack of food. In some cases people feel hungry most of the time and satisfying the constant hunger may cause obesity and even death. This makes no evolutionary sense. Why is a body creating hunger signals when it obviously has more than enough energy in its stores and is obviously consuming more than enough energy to maintain it’s weight? The simple answer is that stored energy is not necessarily available for use, and the amount of energy ingested also does not necessarily reflect the amount of energy available for use.
Whatever the individual cause of obesity is, in the absolute majority of cases, carbohydrate restriction works effectively at reducing adipose tissue weight. This is a common observation in most human and animal studies. Carbohydrate restriction for the most part works because it influences insulin and glucose. In addition it affects our sensations of hunger and satiety and affects the energy flow to the individual tissues. This might be a simplification, but it’s a fair simplification. The increased fat storage and insufficient fat release apparent in overweight must in most cases be explained by the specific disease or condition’s influence on insulin and glucose metabolism, simply because insulin and glucose are the main regulators of fat metabolism.
Exercise and diet are two lifestyle factors with large impact on our imaginary scale. Lifestyle factors do however affect us differently because of our different genetic heritage. Genetic factors may also more easily be understood using a scale model. Looking at fat storage this way, might give us a simple way of explaining many of the often-cited paradoxes of overweight.
One way to find out would be to ask overweight people in a controlled environment to consume as much energy as they want and to expend as much energy as they feel, as long as no carbohydrates are consumed. If our hypothesis is correct, we would expect these people to lose weight while on this diet. To further increase the quality of our data, we could include a control group whose energy intake is equal, but with no restriction in carbohydrate intake.
Our body is immensely complex and in fact a whole range of factors may influence fat storage. The bottom line is that no matter the cause of an increase or reduction in fat mass, it must be explained through its influence on glucose and/or insulin metabolism.
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.