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Brain’s 'hunger hub' could be switched off

11:30am Tuesday 28th April 2015 content supplied byNHS Choices

"Have scientists found a way to banish hunger pangs?," the Mail Online asks. The question is prompted by research in mice looking at the "biological pathways" that regulate appetite and hunger.

While it may feel like the sensation of hunger is triggered by the stomach, it is actually the brain that causes the sensation - specifically, a region of the brain called the hypothalamus.

Experiments found that the brains of hungry mice produce a chemical that targets certain nerve cells. These then stimulate more nerve cells, which promote appetite. The signals to the appetite-stimulating nerve cells can be blocked by the chemical POMC. 

The researchers suggest that this process could be a target for weight loss treatment, possibly in the form of an appetite suppressant. 

However, it is too early to confirm whether this could be a possibility. Biological pathways may be similar in humans, but we don't know if they are exactly the same. Even if further research confirms this pathway as being a key regulator of food intake in humans, no treatment targeting this area has been developed. The researchers used invasive techniques, such as surgery or injections, to manipulate the pathways in mice, rather than drug treatment.

The study furthers the understanding of brain pathways involved in appetite regulation, but the findings have no current implications.


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Where did the story come from?

The study was carried out by researchers from the University of Edinburgh, Harvard Medical School and other US institutions. The study received various sources of funding, including the University of Edinburgh Chancellor's Fellowship and US National Institutes of Health.

The study was published in the peer-reviewed scientific journal Nature Neuroscience.

The Mail Online may have jumped the gun in calling this research a "breakthrough that could help dieters lose more weight". We are a long way from knowing whether a safe and effective treatment could be developed on the back of this research, and even further from knowing whether such a treatment could make dieters "less grumpy".  

The Daily Telegraph's coverage is more restrained and includes some interesting, if over-optimistic, quotes from the researchers themselves. 


What kind of research was this?

This was a laboratory study looking at how appetite is regulated by brain cells in the arcuate nucleus (ARC) of the hypothalamus. The hypothalamus brain region regulates hormone production, keeping our body process in balance; this includes temperature, sleep and appetite. 

The researchers say there are two sets of brain cells in the ARC that work to regulate appetite. Some signal that the body is full, others that the body is hungry and needs to eat. ARC agouti-related peptide (AgRP) increases food intake, while pro-opiomelanocortin (POMC) decreases food intake. It is thought that both control appetite by influencing downstream nerve cells melanocortin-4 receptor (MC4R)-expressing nerves. Previous studies have shown that MC4R nerves have an effect on feelings of fullness and promoting weight loss. These nerves are located in a different part of the hypothalamus - the paraventricular nucleus of the hypothalamus (PVH).

This study used various mice genetically engineered to have functioning or non-functioning versions of these nerves, to further explore the nerve pathways that control appetite in the hypothalamus.


What did the research involve?

The research team used a large number of laboratory experiments in mice to explore in detail the brain pathways involved in appetite and feeding behaviour.

They did a lot of different experiments, which included manipulating brain circuitry through genetic engineering and surgery to measure the effect on energy expenditure, eating habits and other appetite-related behaviour. For example, one of the experiments involved switching off different brain cells by exposing the mice to blue laser light, via an optical fibre implanted into their brains. This allowed them to see what role these brain cells were playing. Other experiments involved manipulating cell function via injections. They also analysed the brains of mice after they'd died.

All the experiments aimed to build a clearer picture of the specific roles of AgRP, POMC and MC4R brain cell signalling in appetite and feeding behaviour. 


What were the basic results?

The researchers found that not having enough energy activates the AgRP cells of the ARC, and this switched off the MC4R nerve cells of the PVH, which drive hunger, appetite and food intake.

MC4R had this effect by activating the lateral parabrachial nucleus (LPBN) pathway. Activating this brain circuit promoted appetite.

Meanwhile, fullness stimulates the POMC cells of the ARC and "switches on" the MC4R cells.

In short, switching MC4R nerve cells off heightened hunger, while turning them on meant they felt full.


How did the researchers interpret the results?

The researchers say that the effects of MC4R nerve cells upon LPBN nerve cells supports this as a brain circuit for suppressing appetite, and highlights this as "a promising target for antiobesity drug development".



This study in mice explored the nerve cell pathways in the hypothalamus that regulate appetite.

It found that hunger drives cells producing a chemical called AgRP to increase food intake. They do this by acting upon MC4R nerve cells in another region of the hypothalamus, which in turn stimulate another nerve cell pathway (LPBN) to stimulate appetite. Meanwhile, another group of nerve cells producing a chemical called POMC block this MC4R pathway when we are full.

The researchers suggest that this MC4R and LPBN pathway could be a target for weight loss treatment. However, it is too early to say if this is a possibility. This laboratory research has only studied mice, and though biological pathways may be similar in humans, we do not know if they are exactly the same. Even if further study identifies the same pathway used in humans, there is currently no treatment to target it. There would be many stages in drug development to go through before it is known whether a treatment could be developed, and then whether it could be safe and effective.

There are techniques you can use to resist the temptation of abandoning your diet goals for the day, such as recognising the triggers, like stress or tiredness, that cause you to overeat. Once you do this, try to find new methods, other than eating, to cope with the triggers.

Read more about "Diet Danger Zones" and how to avoid them

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on TwitterJoin the Healthy Evidence forum.



Links to Headlines

Have scientists found a way to banish hunger pangs? Breakthrough could help dieters lose more weight - and make them less grumpy. Mail Online, April 27 2015

Have scientists found a way to 'switch off' hunger? The Daily Telegraph, April 27 2015

Links to Science

Garfield AS, Li C, Madara JC, et al. A neural basis for melanocortin-4 receptor-regulated appetite. Nature Neuroscience. Published online April 27 2015

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