Joseph Proietto, University of Melbourne
The need to find fuel to generate energy is a profound drive within the biology of all living organisms: we all need food to survive. So it’s not surprising that our bodies have such a complex system to control food intake, driven by hormones.
Hormone levels also change when we lose weight. As much as we battle to trim down via diets and eating patterns, they’re also the reason most of us will regain the weight we lose – or more.
The body’s system for regulating food intake is coordinated by the hypothalamus, which is located under the midline of the brain, behind the eyes:
Within the hypothalamus are nerve cells that, when activated, produce the sensation of hunger. They do so by producing two proteins that cause hunger: neuropeptide Y (NPY) and agouti-related peptide (AGRP).
Quite close to these nerve cells is another set of nerves that powerfully inhibit hunger. They produce two different proteins that inhibit hunger: cocaine and amphetamine-regulated transcript (CART) and melanocyte-stimulating hormone (αMSH).
These two sets of nerve cells initiate and send hunger signals to other areas of the hypothalamus. So, whether you feel inclined to eat or not depends on the balance of the activity between these two sets of neurons.
But what determines which set of neurons dominates at any given time?
The activity is mainly controlled by hormones that circulate in the blood. These come from tissues in various parts of the body that deal with energy intake and storage, including the gut (which receives and digests the food), the fat (which stores the energy) and the pancreas (which makes hormones that are involved in energy storage, such as insulin).
Hormones in the blood
Let’s take a closer look at how each of these blood-circulating hormones work.
Ghrelin is made in the stomach. It stimulates hunger by entering the brain and acting on the neurons in the hypothalamus to increase the activity of the hunger-causing nerve cells and reducing the activity of hunger-inhibiting cells. As the stomach empties, the release of ghrelin increases. As soon as the stomach is filled, it decreases.
Insulin-like peptide 5 (ILP-5) was found to stimulate hunger in 2014. It is the second circulating hormone to have this effect and is mainly produced in the colon. But we still don’t know its physiological role.
Cholecystokinin (CCK) is produced in the upper small bowel in response to food and gives a feeling of fullness. It is released soon after food reaches the small bowel. Researchers have found CCK can stop a mouse from eating as soon as it’s injected into the brain.
Peptide YY, glucagon-like peptide 1 (GLP-1), oxyntomodulin and uroguanilin are all made from the last part of the small bowel and make us feel full. They are released in response to food in the gut.
Leptin is the most powerful appetite-suppressing hormone and is made in fat cells. It was discovered in 1994. The more fat cells we have, the more leptin the body produces.
Amylin, insulin and pancreatic polypeptide are made in the pancreas. Studies in the United States have shown that when insulin enters the brain it inhibits hunger, telling the brain “there is enough energy in the body, take a rest”.
Amylin, discovered in 1981, is made in the same cells that make insulin (the beta cells). It has been shown to inhibit food intake.
The exact role of pancreatic polypeptide is not yet known, but there is evidence that it inhibits hunger.
Once full, the stomach reduces the desire to eat both by lowering ghrelin production and by sending a message to the hypothalamus. Ghrelin levels reach a low around 30 to 60 minutes after eating.
Levels of hormones that make us feel full – CCK, PYY, GLP-1, amylin and insulin – all increase following a meal to reach a peak about 30 to 60 minutes later.
All the hormones then gradually return to their fasting levels three to four hours after a meal.
How weight loss affects our hormones
Several studies have found that diet-induced weight loss is associated with hormone changes that, together, promote weight regain.
Following weight loss, leptin levels decrease profoundly. Other hormonal changes include increases in circulating ghrelin, GIP and pancreatic polypeptide and reductions in PYY and CCK. Almost all of these changes favour regaining lost weight, by increasing hunger, reducing satiety and improving the capacity to store fat. These hormonal changes seem to be present for at least one year after weight loss, leading to a persistent increase in hunger.
These findings suggest suppressing hunger after weight loss – preferably with a replacement of hormones – may help people maintain their new weight.
Several of these agents have recently been approved by different regulatory bodies in the United States, Europe or Canada, but only one – liraglutide – is a version of one of the naturally occurring appetite suppressants (GLP-1). The ideal medication to maintain weight loss would be a long-acting mixture of three or more of the blood-circulating hormones we examined above: leptin, amylin, GLP-1, PYY, CCK and oxyntomodulin.
But producing such a mixture is proving a considerable challenge, so researchers continue to investigate how this might be done.
This article is part of an occasional series, Chemical Messengers, on hormones and the body.
Joseph Proietto is Chair of The medical Advisory Board for Liraglutide 3mg for Novo Nordisk. He receives funding from the NH&MRC.