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Why 'Dieting' backfires: Brain amplifies signal of hunger synapses, finds study

by Max Planck Society

1-hunger - Credit CC0 public domain.jpg

Restrictive dieting (in mice) changes communication in the brain, new research has shown. Nerve cells that mediate the feeling of hunger receive stronger signals, leading to overeating and weight gain after the diet ends - and those signalling changes are persistent.


Restrictive diets - i.e. those that focus on reducing calories - can lead to weight-loss in the short-term, but their limitations are well known, as

(1) they are difficult to maintain, owing to persistent feelings of hunger, and associated changes in mood, energy, cognition and behaviour
(2) they usually lead to 'rebound' effects, so that any weight lost is all too easily regained.

These problems have been amply documented for decades. But this new study, in mice, sheds new light on some of the mechanisms responsible. Results showed that a restricted diet amplifies the signalling of hunger by brain cells in the hypothalamus (a deep brain structure that plays a key role in hormonal signalling and regulation of numerous functions, including appetite and satiety). For details, see:

These changes in the amplification of hunger signals were found to be remarkably long-lasting - reflecting a process called 'synaptic plasticity' (which ultimately underlies all learning and memory).   

According to this press release: 'these findings could help developing drugs to prevent this amplification'.

However, drug-free alternatives for successful long-term weight-loss are already available - involving diets that do NOT focus on calorie-counting, and do not leave people feeling hungry.  Many such examples exist - including a very wide variety of traditional, pre-industrial diets - and they all involve similar principles, namely:

  • eating real food, and avoiding ultra-processed foods, which clinical trials have shown to promote overeating and weight gain. See:
  • reducing sugar and refined carbohydrates, and instead basing meals and snacks on nutrient-dense foods that provide plenty of protein and healthy fats instead. This helps to reduce levels (and surges) of insulin - the key hormone involved in both blood sugar regulation and fat storage.
For an example of a diet (and lifestyle) program along these lines that involves no calorie-counting, and has been successfully piloted in the UK by NHS obesity experts, see:

And the associated book:

See also the latest findings from the general medical practice of Dr David Unwin and colleagues, which also focus on overall nutritional quality of the diet and on keeping insulin levels low, rather than on calorie restriction per se:

Many people who have dieted are familiar with the yo-yo effect: after the diet, the kilos are quickly put back on.

Researchers from the Max Planck Institute for Metabolism Research and Harvard Medical School have now shown in mice that communication in the brain changes during a diet: The nerve cells that mediate the feeling of hunger receive stronger signals, so that the mice eat significantly more after the diet and gain weight more quickly.

In the long term, these findings could help developing drugs to prevent this amplification and help to maintain a reduced body weight after dieting.

"People have looked mainly at the short-term effects after dieting. We wanted to see what changes in the brain in the long term," explains Henning Fenselau, a researcher at the Max Planck Institute for Metabolism Research, who led the study.

To this end, the researchers put mice on a diet and assessed which circuits in the brain changed. In particular, they examined a group of neurons in the hypothalamus, the AgRP neurons, which are known to control the feeling of hunger.

They were able to show that the neuronal pathways that stimulate AgRP neurons sent increased signals when the mice were on a diet. This profound change in the brain could be detected for a long time after the diet.

Preventing the yo-yo effect

The researchers also succeeded in selectively inhibiting the neural pathways in mice that activate AgRP neurons. This led to significantly less weight gain after the diet. "This could give us the opportunity to diminish the yo-yo effect," says Fenselau.

"In the long term, our goal is to find therapies for humans that could help maintaining body weight loss after dieting. To achieve this, we continue to explore how we could block the mechanisms that mediate the strengthening of the neural pathways in humans as well."

"This work increases understanding of how neural wiring diagrams control hunger. We had previously uncovered a key set of upstream neurons that physically synapse onto and excite AgRP hunger neurons.

In our present study, we find that the physical neurotransmitter connection between these two neurons, in a process called synaptic plasticity, greatly increases with dieting and weight loss, and this leads to long-lasting excessive hunger," comments co-author Bradford Lowell from Harvard Medical School.

The findings are published in Cell Metabolism.