When we don’t eat, hunger-inducing neurons in the brain’s hypothalamus start eating bits of themselves (autophagy), sending a hunger signal to prompt eating, researchers at the Albert Einstein College of Medicine have found in experiments with mice.

They said the new findings suggest that treatments aimed at blocking autophagy may prove useful as hunger-fighting weapons in the war against obesity.

New evidence shows that lipids within agouti-related peptide (AgRP) neurons are mobilized following autophagy, generating free fatty acids. Those fatty acids in turn boost levels of AgRP, itself a hunger 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.

The researchers suspect that fatty acids released into the circulation and taken up by the hypothalamus, as fat stores break down between meals, may induce autophagy in those AgRP neurons. However, chronically high levels of fatty acids in the bloodstream, as happens on a high-fat diet, might alter hypothalamic lipid metabolism, setting up a vicious cycle of overfeeding and altered energy balance, the researchers said. Treatments aimed at this pathway might make you less hungry and burn more fat.

The findings might also yield new insight into metabolic changes that come with age, since autophagy declines as we get older, the researchers said.

Ref.: Susmita Kaushik, et al., Autophagy in Hypothalamic AgRP Neurons Regulates Food Intake and Energy Balance, Cell Metabolism, Volume 14, Issue 2, 173-183, 3 August 2011 [DOI: 10.1016/j.cmet.2011.06.008]