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.
In the 1950s, Jean Meyer presented the glcostatic theory. This hypothesis was used (and unfortunately still is) to explain how our blood glucose level controls our sensation of hunger and satiety. It states that a low blood glucose level stimulates an increased hunger and food intake, while high glucose levels will stimulate satiety. The theory is not easily rejected and may indeed seem plausible. In early studies, scientists succeeded in inducing increased food intake in rats and increased hunger in humans, by using insulin to reduce glucose levels. In addition, hypoglycaemia (low blood sugar) in diabetes was known to be associated with increased food intake. Also, the knowledge that our brain is strongly dependant on glucose for fuel further increased the plausibility of the theory. But, although glucose level does influence our feeling of hunger it is however unlikely that it controls our total food intake and low glucose might just be an effect rather than a cause. One good argument against a glucostatic theory is that affecting fat metabolism, independent of glucose levels, can increase hunger.
As we grow our different body tissues grow in unison, but after we become adults most of the change in body size is due to changes in fat tissue size. The lipostatic hypothesis claims that any change in body fat is followed by a signal to either increase or decrease food intake. I’ll admit that from an evolutionary point of view this seems plausible, but the number of observations that fails to be explained by this hypothesis are many. Unfortunately, many consider this hypothesis close to a fact even today, but now it goes under the name of the body weight set-point hypothesis.
One of the strongest arguments in support of the lipostatic hypothesis has been based on the hyperphagia (fancy word for great hunger or eating a lot) and obesity that result following ventromedial hypothalamic (VMH) lesions. During the 40’s and 50’s it was found that damage to specific hypothalamic areas (VMH lesions) provoked dramatic alterations in food intake and body weight. These lesions caused an increased food intake in most animals studied. As it was assumed that the hypothalamus was the control centre of hunger and satiety, the increased food intake in these studies was thus assumed to be a result of increased hunger. Also, people with the genetic condition known as Prader-Willi, are known to have a voracious appetite. This genetic condition affects the hypothalamus as well and it was once again assumed that this genetic error affected the hunger/satiety centre of the brain thus causing increased food intake.
Although VMH lesions were originally used in support of a lipostatic hypothesis, the very same studies provide evidence for the improbability of the same hypothesis. The fact that hunger occurs in rats with VMH lesions despite the presence of an internal excess of metabolic fuels suggests that the size of the fat depots becomes important to feeding only if the animal has access to them. Access is a key point here.
It was later found that although VMH lesions did indeed cause increased food intake, the very same lesions also disrupted fat metabolism in favour of increased fat storage (partly due to increased insulin secretion) thus making fat depots unavailable. Hyperphagia has been associated with obesity and large energy storage in fat tissue, but it has also been shown that in most animal models, the increase in fat storage occurs prior to increases in food intake. In other words, increase in fat storage (the unavailability of fat for fuel) increases hunger and thus food intake. This is an extremely important point. Increased hunger may very likely be caused by increased fat storage and not the other way around, as is the general interpretation. In support of the above-mentioned, scientists has successfully increased both the power and the duration of satiety, simply by inhibiting fat storage.
Even in the Prader-Willy syndrome, the hyperphagia observed might very well be secondary to fat storage. They might be eating because they are getting fat, and not the other way around. They might be eating because most energy is locked away in fat depots, and the rest of the body is starving. Our body gets its energy either from its stores or from food. If the stored energy is unavailable the body is left with no other choice than to increase hunger. I have unfortunately only seen one study described where a low carbohydrate diet was administered to people with Prader-Willi, but it does provide some interesting clues. Remember that reducing dietary carbohydrates most often will cause a decrease in fat storage. If hunger is caused by large fat storage, reducing the storage would presumably decrease hunger, as has been done with medications in other studies. In the study described in ”The Prader-Willi syndrome”, by Holm et al it seems that carbohydrate restriction does indeed reduce hunger effectively, even in people with Prader-Willi. The mechanism behind the reduction in hunger is presumably the decrease in fat storage and thus an increased release of stored energy from fat tissue.
In the genetic rat models of obesity fa/fa rats and ob/ob rats, their defect genetics makes them overweight even with calorie restriction. The effect of their defects is an increased fat deposition. This increased storage of energy in fat tissue causes a concomitant hyperphagia and decreased energy expenditure.
Low blood sugar may also provide a strong stimulus for hunger, as the glucostatic theory claims. But, the reason for a fall in glucose levels may be caused by a low fat oxidation. If little fat is oxidized and ketone bodies are not being produced our body is more dependant of glucose for fuel, and blood sugar falls quickly. In the studies where insulin was used to stimulate hunger, it also stimulated fat storage. Insulin makes all fuels less available fore use.
It may not even be the low glucose level in it self that makes us hungry. It may simply be the low total amount of energy available. A combined inhibition of fatty acid and glucose metabolism produces a far greater eating response than would be expected from inhibiting the metabolism of each component separately. A combined inhibition may even produce hunger when the metabolic inhibitors are given in doses that alone do not stimulate eating. This increase in food intake would not be expected if signals from glucose and fat metabolism controlled feeding independently, and indicates that changes in glucose and fat metabolism influence feeding through a common mechanism. The likely place for this regulation would be the liver.
Mark I. Friedman and Edward Stricker elucidated the mechanisms of how macronutrient composition affects hunger as early as 1976. They wrote that the stimulus for hunger and satiety were likely the result of alterations in oxidative metabolism within the liver. Their reasoning makes unnecessary previous hypothesis such as hunger and satiety centres, glucostat, lipostat, and body weight set point.
More recent work by Mark Friedman makes it clear that liver ATP production is an important regulator of hunger. Although intake of the different macronutrients affects hunger it doesn’t seem likely that quantitative changes in the use of these nutrients would provide a stimulus for hunger. Compensatory changes in the use of other fuels would limit the significance of this. It is more likely that hunger occurs whenever the immediate availability of utilizable metabolic fuels is reduced below some critical level.
The consequence of all this is that a diet with little carbohydrates and generous amounts of fat makes us lean much because this diet provides a constant flow of available energy for the liver, both from food intake and from body energy stores, and this makes us less hungry.
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