SAN JOSE, Calif. – When the clock strikes noon and office microwaves commence nuking lunches across the nation, it’s because our grumbling stomachs insist that we eat. And while researchers know which signals control how hungry we feel — specific proteins in our brains — they’re still searching for what sets those signals off.

Now, Rajat Singh and his colleagues at the Albert Einstein College of Medicine at Yeshiva University in New York may be one step closer with a study published online last week in the journal Cell Metabolism.

When Singh and his co-authors studied mice, they discovered that the brain cells responsible for controlling hunger, called AgRP neurons, started to consume small parts of themselves when the body had gone without food for several hours. That process, called autophagy, set off a chain reaction that boosted hunger proteins in the brain.

“The biology in mice very closely mimics human biology,” said Singh — including the way our brains are regulated. Studying how mouse brains work is one of the ways in which the research community gains insights into how our own brains function. If scientists can learn to control this cannibalistic behavior in these cells, they can develop treatments that will help with obesity and overfeeding in humans, said Singh.

In this case, “understanding the regulation of AgRP neurons is critical because these neurons are sufficient to orchestrate voracious eating,” said Scott Sternson, a scientist who studies how our brains are wired at the Janelia Farm Research Campus of the Howard Hughes Medical Institute, who wasn’t involved in the study. At the moment, there’s no known way of disrupting autophagy, said Fredric Kraemer, professor of medicine at Stanford University who also wasn’t involved in the study.

There is a huge network of brain cells that must talk to each other in order to regulate hunger in humans, Singh said. These cells must coordinate signals from all over the body about nutrient and energy levels, and then relay instructions to other areas such as our muscles to start or stop eating.

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The wizard behind the curtain that controls all this activity is a tiny region just above the brain stem called the hypothalamus. But researchers didn’t have a good understanding of what regulated these neurons, Sternson said. “We all have a basal level of autophagy happening all the time,” said Singh.

Normally, this low level of self-consumption is how our cells clear out damaged parts or get rid of things they no longer need, said Singh. “At baseline, it’s a garbage system, a housekeeping function.” But when we’ve gone without food for several hours, our body starts to break down its fat reserves, called triglycerides, into fatty acids, Kraemer said.

When the hypothalamus registers an increase in circulating fatty acids, the cells that control hunger rev up their autophagy process, Singh said.

This process breaks down the neuron’s fat reserves, releasing fatty acids to float freely around the cell. This triggers production of the proteins that tell us we’re hungry, Singh said.

 


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