When a dieter starves themselves of calories, they starve their brain cells as well. New research finds that these hungry brain cells then release "feed me" signals, which drive hunger, slow metabolism and may cause diets to fail.

When the researchers created mice whose brain cells couldn't send out the signals, or appetite-increasing proteins, and these mice were leaner and ate less than normal after being starved.

"We generated a mouse that lacked this process in these neurons," study researcher Rajat Singh, of Albert Einstein College of Medicine in the Bronx, New York, said. "What we find is these mice eat less in response to a starvation challenge; they are leaner and they are healthier."

The results likely would apply to humans, as mice are often used as biological models for us, the researchers say; even so, further research is needed to confirm the same process occurs in humans. [7 Diet Tricks that Really Work]

Starving the brain

The starvation mechanism and feelings of hunger produced by these neurons is signaled through a process called autophagy, (which literally means "self-eating") in which the cell breaks down its used parts. They do this to recycle the used parts, but also to harvest energy from them.

Most brain cells keep their autophagy at a steady level and don't respond to starvation. These appetite-sensing neurons are different, the researchers found, and are now the only known brain cells to ramp up autophagy in times of starvation.

This increased breakdown increases cellular levels of compounds called free fatty acids. Higher levels of fatty acids signal these special brain cells to release the appetite-inducing protein, which is called agouti-related peptide (AgRP).

"These neurons sense nutrients in the body and tell the body it's time to eat, time to stop eating," Singh told LiveScience. "When you are hungry, there is this process in the brain that gets upregulated and that makes you eat."

Turning down appetite

When the researchers turned off autophagy in the hypothalamus of mice, AgRP levels stayed low, as did levels of free fatty acids. These changes stopped the hunger signaling during times of starvation. When compared with normal mice, the mutant mice were about 10 percent leaner, were able to burn more energy, were more active and also ate less after food was withheld.

Because this AgRP protein is only expressed in these appetite-controlling neurons, blocking this process should only affect the appetite signaling, not the cellular breakdown and use of stored energy in other parts of the body.

If the process works the same way in humans as it does in mice, interrupting this pathway could help curb hunger and obesity. The researchers are continuing to study these mice and how disrupting this pathway changes their eating habits.

"These mice eat less in response to a starvation challenge, they are leaner and they are healthier," Singh said. "It has tremendous relevance to fighting obesity."

The study was published yesterday in the journal Cell Metabolism.

This article was reprinted with permission from LiveScience.

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