By Bronwyn Thompson
March 26, 2023
A change in the brain’s neural pathways while dieting facilitates rebound weight gain Depositphotos
Anyone who has achieved it knows that maintaining weight loss long-term is an uphill battle. The hormonal, metabolic and neural factors that regulate body weight means it can be more a matter of biology than willpower. At the same time, the global weight loss industry is valued at US$224 billion and is set to grow to $405 billion by 2030.
One of the most frustrating aspects for many is the yo-yo effect of calorie restriction, that sees dieters regain half of their lost pounds within two years, and around 80% after five. This is often seen as a personal failure and can have long-lasting physical, emotional and psychological impacts.
But it may not be all doom and gloom. Researchers from the Max Planck Institute for Metabolism Research (MPIMR) and Harvard Medical School have identified a significant change in neural pathways in the brain that occurs when dieting, with much stronger signals traveling to the nerves that mediate feelings of hunger. Inhibiting these signals may help scientists develop treatments that better assist people in maintaining their weight.
“People have looked mainly at the short-term effects after dieting,” said Henning Fenselau, a researcher at MPIMR, who led the study. “We wanted to see what changes in the brain in the long term.”
To do so, the researchers put mice on a diet and monitored brain circuitry, focusing in on the Agouti-Related Peptide (AgRP) neurons in the hypothalamus, known to control feelings of hunger. Previous studies have shown how stimulating these neurons leads to acutely elevated food consumption. They found that the neuronal pathways to the AgRP neurons amplified when the animals were on the diet and remained at those amplified levels, resulting in extreme hunger signals that led to greater food intake and quicker weight gain.
“This work increases understanding of how neural wiring diagrams control hunger,” said co-author Bradford Lowell from Harvard Medical School. “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.”
When the researchers inhibited the connection between those neurons, AgRP activity decreased and the animals had a more regulated response to food intake. Not surprisingly, this led to significantly less weight gain.
“This could give us the opportunity to diminish the yo-yo effect,” said 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.”
The study was published in Cell Metabolism.
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