Understanding how appetite is regulated throughout life remains elusive

Diet and lifestyle 14. jan 2021 3 min Professor Jens Juul Holst Written by Kristian Sjøgren

European researchers carried out a major study on how age as well as sex, nationality and weight affect the regulation of appetite through four hormones.

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Food intake and obesity are clearly linked: you gain weight if your energy intake is more than the energy you consume. But what makes this happen?

Since more and more people are becoming obese, with an increased risk of various diseases from diabetes to cancer, researchers are very interested in understanding the mechanisms that encourage our hands to stuff too much food in our mouths – even after we no longer need it.

For this reason, a major collaboration involving researchers from across Europe has sought to establish how appetite is regulated differently according to age as well as sex, nationality and weight.

The research tried to achieve this by examining how many factors influence the levels of appetite-regulating hormones.

“Elucidating this topic is extremely important to improve insight into how people eat too much and become overweight. Understanding the body’s mechanisms will enable us to develop drug treatments for obesity, and this could reduce many people’s risk of developing various related diseases. This was the focus of this research project,” explains Jens Juul Holst, Professor, Department of Biomedical Sciences, University of Copenhagen.

The research results have been published in Nutrients.

Several hormones control hunger

Four hormones largely regulate our appetite and hence the risk of obesity: glucagon-like peptide 1 (GLP-1), peptide YY (PYY), leptin and ghrelin. The first three reduce appetite after a meal, and ghrelin is the only hormone known to stimulate our appetite.

Some types of diabetes and obesity drugs target the GLP-1 system, including Novo Nordisk’s semaglutide, a GLP-1 receptor agonist.

PPY is secreted in the intestines and increases the feeling of satiety.

Leptin is released by fat cells and also reduces appetite. Some people have diseases that cause leptin to malfunction, and they cannot feel full, eat constantly and thus become extremely obese.

Drug developers have tried to develop drugs targeting leptin for many years, but all attempts have failed.

391 participants

The new study involved 391 participants from Scotland and Greece. The participants consumed four liquid test meals on four days that contained different quantities of protein and calories according to the participants’ needs.

Some of the test meals contained the equivalent of the participants’ normal energy consumption, and others contained 40% more energy than they could use.

The researchers examined every day how the four appetite-regulating hormones changed when the participants consumed the various test meals and the differences between groups.

The researchers also asked the participants to describe how full they felt after the various test meals.

The participants were categorized by age, sex, nationality and weight to determine whether these factors made any difference.

“This was a very large study run by a well-funded consortium. There were therefore also high expectations for the results,” says Jens Juul Holst.

No pioneering results

However, the results did not fulfil the expectations.

The Danish researchers in the consortium found that the levels of ghrelin in the gut declined after a meal.

“This was expected, because ghrelin increases hunger, but unfortunately this was also the only conclusive result,” explains Jens Juul Holst.

The four age groups differed: the oldest participants had less appetite, ate less and generally secreted more GLP-1 and PYY in the gut.

The other studies did not result in noteworthy results.

“The study is very descriptive and shows what happens without being able to explain how. But we found that age reduces appetite and elevates the release of hormones that reduce appetite at meal times. This can be a health problem, because older people may have difficulty eating enough, and this is unhealthy,” says Jens Juul Holst.

Obesity costs society

Jens Juul Holst says that advancing knowledge on how various factors affect the risk of becoming overweight is very important.

The prevalence of obesity looks especially troublesome among middle-aged men, with more than half being overweight in many countries.

According to Jens Juul Holst, this is a huge problem because overweight is unhealthy for the individual and a huge burden for society.

“Fat and happy is pure nonsense. So many diseases are associated with overweight that it puts society under enormous pressure. That is why it is so interesting to determine how these hormones affect the risk of becoming obese and how we might be able to manipulate them to prevent this from happening,” explains Jens Juul Holst.

Intensive research on hormones

Jens Juul Holst says that various groups of researchers and drug developers are working on regulating appetite and obesity by manipulating these four hormones.

Novo Nordisk is focusing on GLP-1 receptor agonists, and their semaglutide studies represent the best results in this field so far.

In Novo Nordisk’s clinical trials, participants lost an average of 18% of their body weight within a year.

The latest research also focuses on how bariatric surgery enables people to lose weight. One might think that the reason is that they cannot fit as much food in their stomachs. However, the research suggests that this effect is probably linked to changes in the levels of the four hormones.

“Researchers are trying to determine which hormone is the most important, so treatments can be tailored to that one. Making drugs targeting PYY is difficult technically, and experiments have shown that leptin is not promising. Novo Nordisk has had great success with GLP-1, and ghrelin looks very interesting. If we can use antagonists to counteract the effect of ghrelin, this may also become a very promising target for obesity drugs, because ghrelin also correlates best with the way the brain regulates appetite,” says Jens Juul Holst.

Jens Juul Holst has pioneered the isolation and characterization of GLP-1 and discovery of the potential of GLP-1 for treatment of diabetes and obesit...

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