Biologists have identified several hormones that play a key role in eating and the way our body uses energy and stores fat.  These hormones include cortisol, insulin, leptin, and ghrelin. In spite of research that shows that these hormones let us know when we are hungry and when we have had enough food, there is still doubt as to their role in obesity.

Another theory is that obesity may be the result of a genetic predisposition. It seems that body size runs in families. Having one obese parent results in a 40 percent chance of becoming obese, and having two obese parents increases the likelihood of becoming obese to 80 percent.

The role of hormones

One biological theory of over-eating and obesity is that there is an imbalance of hormones. As you will see in the chart below, there are several hormones that play a role in our eating behaviour.  Being able to isolate a single hormone to argue that it plays a key role in obesity has not yet been possible. It is highly likely that all of these hormones may play a key role and even more likely that there is some level of interaction of the hormones.

Ghrelin tells us that we need to eat. When glucose levels in the blood fall, ghrelin levels rise, telling the brain that we need to eat to get more energy.  Could this hormone play a role in obesity?

Interestingly, ghrelin levels are lower in individuals with a higher body weight compared with lean individuals, which suggests ghrelin could be involved in the long-term regulation of body weight. One would expect higher levels in people with obesity. However, ghrelin levels are usually lower in people with higher body weight compared with lean people, which suggests ghrelin is not a cause of obesity, but may influence eating behaviours that may contribute to obesity.

Goldstone (2010) carried out a study with 22 nonobese adults (17 men and 5 women). The design was a repeated measures design where the participants either skipped breakfast or came to the lab 90 minutes after eating breakfast. In the case where participants came to the lab after having eaten breakfast, on one visit they were injected with a saline solution and on another visit they were injected with ghrelin. The experiment was a double-blind control where neither the researcher nor the participants knew which injection was given.

In each condition, the participants were shown pictures of high-calorie foods such as chocolate cake and pizza. They were also shown low-calorie foods such as salads, vegetables, and fish. Using a keypad, the participants were asked to rate how appealing they found each food picture. Overall, the high-calorie foods were more appealing in all conditions. However, high-calorie foods, especially sweet foods, were of greater appeal when the participants fasted and when they received ghrelin after eating breakfast. But we know that ghrelin makes us hungry, so why does this matter?  What may matter is both why ghrelin levels may increase and what we choose to eat when our ghrelin levels of high.

Research has shown that cortisol may play a key role in the increase in ghrelin (for example, Azzam et al, 2017). This may mean that stress and sleep deprivation - both of which raise one's level of cortisol - may play a role in increased ghrelin levels (and decreased leptin levels) and therefore unhealthy eating patterns. Brondel et al (2010) carried out a study to see what the short-term effects of sleep deprivation would be on men's eating behaviour. The participants were 12 men with an average age of 22 years old and an average BMI of 22.30. The design was a repeated measures design where there were 48 hours between conditions.

In one condition, the men slept for eight hours - from midnight to 8 am - or for four hours - from 2 am - 6 am. Their eating behaviour was then observed over the next day.  They were given jam on buttered toast for breakfast, a buffet for lunch, and a menu for dinner from which they could order whatever they wanted. In addition, their physical activity was measured by using an actimeter.

The researchers found that when the men slept only four hours, they consumed on average 22% more calories on the following day than when they had eight hours of sleep. They also found that physical activity was slightly higher for those with sleep deprivation as well. The researchers concluded that poor sleep hygiene over time could lead to a higher calorie intake than energy expenditure and could be a factor in obesity.

Leptin is the hormone that tells us that we are done eating. It gives us the feeling of being full - what biologists refer to as satiety. As our fat cells decrease because we have used up energy, our leptin levels fall (and ghrelin levels rise).  When our leptin levels fall, it gives us a feeling of hunger and tells us that it is time to eat. As we eat, our body then will begin to store some of the energy as fat.  As the fat cells increase, the leptin levels rise and signal to the hypothalamus that we feel full (or satiated). At this point, we then stop eating and the cycle begins all over again.  So, if this is a normal process, how might it play a role in obesity?

Biologists argue that leptin resistance may play a role in obesity.  Leptin resistance is the failure of leptin to signal to the hypothalamus that feeling of satiety, indicating that eating should stop. It is still not clear what exactly leads to leptin resistance; it is believed that there may be many different reasons why leptin resistance may occur. Knight et al (2010) found that when mice were given a high fat vs low-fat diet from the age of 4 weeks old, those on the high-fat diet developed leptin resistance and became obese. The difficulty is determining whether this is true also in humans.  Does leptin resistance lead to obesity?  Or does obesity potentially lead to leptin resistance? 

 Teacher only box

Based on your understanding of statistics, do you think that they should hurry to approve the drug?

As can be seen in the presentation, the problem with these results is that they rely on the mean of the weight lost. In the high-dose group, the range of results was from a loss of 15 g to a gain of 5 kg. In addition, body mass that was lost was regained quickly after the study.

Do a quick look online at all of the possible leptin supplements that you could buy.  What would you advise a friend who thinks that this may be the solution they have been looking for?

Most leptin supplements don’t actually contain the hormone. While numerous supplements are labeled as “leptin pills,” most contain a mix of various nutrients marketed to reduce inflammation and, therefore, increase leptin sensitivity.

The research on the role of leptin is rather mixed.  In addition, there are clearly other ways that we can lose weight that are more natural - e.g. exercise, controlling our sugar intake. The goal of this discussion or writing task is to get students to think about the use of such supplements and to build a coherent argument for or against their use.

Genetic explanations

In order to investigate the relative role of genes and the environment, researchers can carry out twin studies. Stunkard et al (1990) studied 93 pairs of MZ twins who were raised apart. He found a concordance rate of over 65% for BMI. This means that there may be a genetic predisposition to obesity that is expressed through environmental stimuli. Although results from twin studies indicate a genetic factor in obesity, the role of this factor is not really clear. One suggestion relates to metabolism, which may be genetically determined, but the evidence is still inconclusive.

Sorensen et al (1998) carried out a study of Danish children who had been adopted.  The study was a longitudinal study, following the children over a period of 23 years. The researchers found a greater correlation between the weight of the adoptees and the birth parents than between the adoptees and the adoptive parents.  This seems to indicate a genetic link to obesity.  However, the influence of the mother's eating habits and the early environment after birth and before the adoption took place cannot be ruled out.

Linkage analysis studies have found a link between a mutation of a gene encoding POMC (proopiomelanocortin) and obesity. POMC is associated with appetite regulation. A study by Farooqi and O'Rahilly (2006) was carried out with mice. They found that mice with a mutation of the POMC gene showed higher levels of appetite and obesity. However, this was only true when they were given a high-fat diet.  When they were given a balanced diet, their weight was within the range of normal.  This could be evidence of gene-environment interaction - that is, that the presence of the genetic mutation alone is not enough to cause obesity; it must be expressed by a certain type of diet.  As promising as this research may appear, only about 5% of people with obesity have this genetic mutation (Bouchard, 2009).

There is evidence that genes may determine individual susceptibility to weight gain. However, the obesity epidemic cannot be attributable to genetic factors alone, since the increase in the prevalence of obesity has taken place over too short a period for the genetic make-up of the population to have changed substantially. Changes in culture and food availability - together with this genetic predisposition - may explain the steep increase in obesity worldwide.