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Weight Loss

How to Short Circuit Hunger

Hunger ensures survival by signaling to the body that energy reserves are low and food is needed to avoid starvation. However, anyone who has ever tried to lose weight knows that it’s no fun to feel hungry. In fact, the drive to tame gnawing hunger pangs can sabotage even the best-intentioned dieter. But how exactly is it that fasting creates these uncomfortable feelings – and consuming food takes them away?

Working to unravel the complex wiring system that underlies this intense physiological state, investigators at Beth Israel Deaconess Medical Center (BIDMC) in Boston and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institutes of Health (NIH), have identified a long-sought component of this complicated neural network. The study was published April 27th 2015 online in Nature Neuroscience.

A release from Beth Israel explains that the team has found that a melanoncortin 4 receptor-regulated (MC4R) circuit serves as the neural link that inhibits and controls eating. Their discovery shows that this brain circuit not only promotes fullness in hungry mice but also removes the almost painful sensation of grating hunger, findings that could provide a promising new target for the development of weight-loss drugs.

The Roots of Hunger

The release quotes co-senior author Bradford Lowell, MD, PhD, an investigator in BIDMC’S Center for Nutrition and Metabolism and Professor of Medicine at Harvard Medical School, as saying, “One reason that dieting is so difficult is because of the unpleasant sensation arising from a persistent hunger drive,” explains the study’s “Our results show that the artificial activation of this particular brain circuit is pleasurable and can reduce feeding in mice, essentially resulting in the same outcome as dieting but without the chronic feeling of hunger.”

The Lowell laboratory has spent the last two decades creating a wiring diagram of the complex neurocircuitry that underscores hunger, feeding and appetite. Their group, along with others, made the key discovery that Agouti-peptide-expressing (AgRP) neurons, a small group of neurons located in the brain’s hypothalamus, detect caloric deficiency and drive intense feeding.

“When these AgRP neurons are ‘turned on,’ either by fasting or by artificial means, laboratory animals eat voraciously,” says Lowell. What’s happening, he explains, is that AgRP neurons sense the low energy reserves, become activated, and through the release of inhibitory neurotransmitters, suppress the activity of downstream neurons, which are responsible for feelings of fullness, or satiety. This causes hunger.

But to understand exactly how the brain regulates appetite, the researchers needed to determine which neurons were downstream of the AgRP neurons and were actually causing the activation and inhibition of hunger.