Why diets don't work? Starved brain cells eat themselves

A report in the August issue of the Cell Press journal Cell Metabolism might help to explain why it's so frustratingly difficult to stick to a diet. When we don't eat, hunger-inducing neurons in the brain start eating bits of themselves. That act of self-cannibalism turns up a hunger signal to prompt eating.

"A pathway that is really important for every cell to turn over components in a kind of housekeeping process is also required to regulate appetite," said Rajat Singh of Albert Einstein College of Medicine.

The cellular process uncovered in of the brain's hypothalamus is known as autophagy (literally self-eating.) Singh says the new findings in mice suggest that treatments aimed at blocking autophagy may prove useful as hunger-fighting weapons in the war against .

The new evidence shows that lipids within the so-called agouti-related peptide (AgRP) neurons are mobilized following autophagy, generating . Those fatty acids in turn boost levels of AgRP, itself a signal.

When autophagy is blocked in AgRP neurons, AgRP levels fail to rise in response to starvation, the researchers show. Meanwhile, levels of another hormone, called -melanocyte stimulating hormone, remain elevated. That change in body chemistry led mice to become lighter and leaner as they ate less after fasting, and burned more energy.

Autophagy is known to have an important role in other parts of the body as a way of providing energy in times of starvation. However, unlike other organs, earlier studies had shown the brain to be relatively resistant to starvation-induced autophagy.

"The present study demonstrates the unique nature of hypothalamic neurons in their ability to upregulate autophagy in response to starvation that is consistent with the roles of these neurons in feeding and energy homeostasis," the researchers wrote.

Singh said he suspects that fatty acids released into the circulation and taken up by the as fat stores break down between meals may induce autophagy in those AgRP neurons. Singh's research earlier showed a similar response in the liver.

On the other hand, he says, chronically high levels of fatty acids in the bloodstream, as happens in those on a high-fat diet, might alter hypothalamic metabolism, "setting up a vicious cycle of overfeeding and altered energy balance." Treatments aimed at the pathway might "make you less hungry and burn more fat," a good way to maintain energy balance in a world where calories are cheap and plentiful.

The findings might also yield new insight into metabolic changes that come with age given that autophagy declines as we get older. "We already have some preliminary evidence there might be changes with age," Singh said. "We are excited about that."

add to favorites email to friend print save as pdf

Related Stories

Research on obesity targets the brain's use of fatty acids

Jan 04, 2011

Researchers at the University of Colorado School of Medicine have created a new and exciting mouse model to study how lipid sensing and metabolism in the brain relate to the regulation of energy balance and body weight. The ...

DREADD-ing your next meal

Mar 01, 2011

In the face of the growing obesity epidemic, much research has focused on the neuronal control of feeding behavior. Agouti-related protein (AgRP) neurons express three proteins that have been implicated in changes in energy ...

Neurons show sex-dependent changes during starvation

Jan 16, 2009

When it comes to keeping brains alive, it seems nature has deemed that females are more valuable then males. As reported in this weeks' JBC, researchers found that nutrient deprivation of neurons produced sex-de ...

Researchers discover new fat-fighting pathway

Apr 01, 2009

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered a process that controls the amount of fat that cells store for use as a back-up energy source. Disruption of this process ...

Cell recycling protects tumor cells from anti-cancer therapy

Mar 06, 2008

Cells have their own recycling system: Discarded cellular components, from individual proteins through to whole cellular organs, are degraded and the building blocks re-used in a different place. The scientific term for this ...

Recommended for you

Organovo has 3D-printed liver tissue for drug testing

Nov 20, 2014

(Medical Xpress)—The commercial release of 3D printed liver tissue was announced earlier this week. Organovo is the company behind the release. The product is intended for use for preclinical drug discovery ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.