Leptin communicates with the brain’s reward system in several ways

Breaking new ground 18. jan 2022 2 min Professor Suzanne Dickson Written by Kristian Sjøgren

Researchers have identified two additional signalling pathways through which leptin regulates food intake by modulating the motivation to obtain food.

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Have you ever wondered why resisting food is very difficult when you are hungry?

One reason is that dopamine cells in the brain’s reward system become activated, and this powerfully drives us to find food and eat it.

Several metabolic hormones that control appetite are known to regulate dopamine cells. One of these is leptin, discovered in 1994, which is produced by fat tissue. Leptin informs the brain about how much fat we have and puts a brake on overeating by inhibiting the parts of the brain controlling hunger and also the reward system.

The research, published in Biological Psychiatry, provides new insight on how leptin communicates with the dopamine system.

“We had an incomplete picture of how leptin helps to regulate the reward obtained when eating food. Scientists already know that leptin suppresses food intake by directly influencing the dopamine system. What is new is that we have identified two indirect pathways by which leptin controls food reward behaviour. The results show how important leptin signalling is, since it engages several pathways to exert the overall effect,” explains a researcher behind the study, Suzanne Dickson, Professor, Department of Physiology, University of Gothenburg, Sweden.

Leptin suppresses the dopamine reward system

Dopamine is a signal involved in motivating us to seek out things we find pleasurable and tempting when hungry. When we eat, we feel good and this encourages us to eat more. This is an evolutionary mechanism nature uses to constantly ensure that the body has enough energy and that the food contains many nutrients.

However, this is only one aspect of the situation.

Leptin is secreted in fat tissue and inhibits the drive to eat. Therefore, in theory, the more overweight a person is, the more leptin they produce and the less appetite drive they should have. This part of the system should help to ensure that people do not automatically continue to eat more than they need for energy purposes.

Suzanne Dickson points out, however, that this system does not seem to work among people with obesity.

“Obese people become resistant to leptin, so it no longer reduces their drive to eat. Part of the challenge associated with the trend in the growing number of obese people worldwide is understanding what happens when leptin signalling does not function as it should,” says Suzanne Dickson.

Using advanced genetics to manipulate mouse brains

To discover more about leptin signalling, the researchers worked with transgenic mice, which enabled them to use chemogenetics to visualise and control the response of the pathways regulated by leptin.

Chemogenetics is an advanced technology for specifically revealing the function of brain pathways, especially in mice. The technique involves using viruses to deliver a designer receptor to a group of nerve cells and later determining how behaviour is altered when the mice are treated with a designer ligand for that receptor.

It may be early days, but there is hope that chemogenetics could be used to control populations of neurons in humans: for example, helping to stop the activation of cells that cause seizures among people with epilepsy. At least in mice, we now know more about the pathways driving us to eat, thanks to this cutting-edge approach.

“Giving the experimental animals leptin targets all the cells in their brain. With chemogenetics, we can study how leptin affects small subgroups of neurons. Then we can track back to determine what these neurons are connected to. Understanding how leptin communicates with the brain’s reward system is important because this determines which signalling pathways are dysfunctional when people develop eating disorders, including those that lead to obesity,” explains Suzanne Dickson.

May be relevant for treating eating disorders

The results revealed two indirect signalling pathways through which leptin affects the brain and the drive to eat.

Suzanne Dickson says the discovery is useful in understanding what happens to the signalling to, and in the brain when people with obesity do not stop eating soon enough.

Even more interesting, according to Suzanne Dickson, is what the discovery may mean for people with anorexia.

“Leptin can very likely modify some of the clinical observations associated with anorexia nervosa. If we find better ways to control the pathways regulated by leptin, this may help reduce the symptoms of this disease. Pathways involved in controlling food intake and motivation are relevant for all sorts of eating disorders,” concludes Suzanne Dickson.

Identification of novel neurocircuitry through which leptin targets multiple inputs to the dopamine system to reduce food reward seeking” has been published in Biological Psychiatry. In 2018, the Novo Nordisk Foundation awarded a grant to Suzanne Dickson for the project Deciphering Food Cue– and Ghrelin-responsive Neurons that Cause Overeating.

Our main focus is to unravel the neuronal pathways responding to environmental and intrinsic signals that regulate feeding behaviours - Gut-brain axi...

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