Summary: When dieting, hunger-mediating AgRP neurons receive stronger signals, inducing synaptic plasticity. This may explain why people tend to eat more after a diet and regain the weight they have lost.
Source: Max Planck Institute
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.
About this synaptic plasticity and diet research news
A synaptic amplifier of hunger for regaining body weight in the hypothalamus
Weight loss upon caloric deprivation activates PVHTRH neurons that co-express PACAP
Activated PVHTRH neurons increase the number of active PVHTRH → AgRP neuron synapses
Potentiation of excitatory PVHTRH → AgRP synapses lasts until lost weight is regained
PVHTRH → AgRP circuit activity is necessary and sufficient for driving weight (re)gain
Restricting caloric intake effectively reduces body weight, but most dieters fail long-term adherence to caloric deficit and eventually regain lost weight.
Hypothalamic circuits that control hunger drive critically determine body weight; yet, how weight loss sculpts these circuits to motivate food consumption until lost weight is regained remains unclear.
Here, we probe the contribution of synaptic plasticity in discrete excitatory afferents on hunger-promoting AgRP neurons.
We reveal a crucial role for activity-dependent, remarkably long-lasting amplification of synaptic activity originating from paraventricular hypothalamus thyrotropin-releasing (PVHTRH) neurons in long-term body weight control. Silencing PVHTRH neurons inhibits the potentiation of excitatory input to AgRP neurons and diminishes concomitant regain of lost weight.
Brief stimulation of the pathway is sufficient to enduringly potentiate this glutamatergic hunger synapse and triggers an NMDAR-dependent gaining of body weight that enduringly persists.
Identification of this activity-dependent synaptic amplifier provides a previously unrecognized target to combat regain of lost weight.