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 this 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,” including the way our brains are regulated, Singh said. 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, Singh said.
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. Sternson was not involved in the study.
However, there currently is 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 about nutrient and energy levels from all over the body, then relay instructions to other areas such as our muscles to start or stop eating.
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, said Sternson.
“We all have a basal level of autophagy happening all the time,” Singh said. Normally, this low level of self-consumption is how our cells clear out damaged parts or get rid of things they no longer need, he added. “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, said Singh.
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, said Singh.
Irfan Rydhan, a 36-year-old San Jose resident, is familiar with the hunger signals emanating from his brain. He is observing the Muslim holy month of Ramadan, when he must refrain from eating and drinking between sunrise and sunset.
Getting through the day is very much an exercise in willpower and self-discipline.
“I try to avoid watching TV while I’m fasting because there’s a lot of commercials about food,” Rydhan said. You don’t really notice how many there are until you start, he said.
Fasting during Ramadan is one of the five pillars of Islam. It’s a way of purifying both the spirit and the body, Rydhan said.
He eats a meal high in protein before sunrise, and then breaks his fast after sunset with a small meal called iftar.
The autophagy induced by fasting is probably at its peak after seven or eight hours of not eating, Singh said, which means hunger signals are also high during this time.
Rydhan tries not to overdo it during the evening meal, but he isn’t always successful. “We’re human and we make mistakes, but we try our best,” he said.
Contact Jane J. Lee at 408-920-5064.
