Researchers locate brain cells that drive appetite in obesity

Researchers at the Garvan Institute of Medical Research have discovered a group of brain cells that boost appetite when there is a prolonged surplus of energy in the body, such as excess fat accumulation in obesity. Writing in the journal Cell Metabolism, the researchers noted that these cells not only produce the appetite-stimulating molecule NPY, they also make the brain more sensitive to the molecule, boosting appetite even more.

Obesity is a major public health issue and a disease that affects more than one in 10 adults and increases a person’s risk of developing other chronic conditions, such as diabetes or heart disease. While many factors can influence the development of obesity — an excessive accumulation of fat tissue in the body — eating patterns and physical activity levels are key contributors.

“Our brain has intricate mechanisms that sense how much energy is stored in our body and adjust our appetite accordingly,” said Professor Herbert Herzog, senior author of the study and Visiting Scientist at Garvan. “One way it does this is through the molecule NPY, which the brain produces naturally in response to stresses, such as hunger, to stimulate eating.

“When the energy we consume falls short of the energy we spend, our brain produces higher levels of NPY. When our energy intake exceeds our expenditure, NPY levels drop and we feel less hungry. However, when there is a prolonged energy surplus, such as excess body fat in obesity, NPY continues to drive appetite even at low levels. We wanted to understand why.”

In mouse models of obesity, the researchers investigated cells in the brain called neurons that produced NPY and discovered that, surprisingly, 15% of them were different — they did not shut down NPY production during obesity.

“We found that under obese conditions, appetite was mostly driven by NPY produced by this subset of neurons,” Herzog said. “These cells did not only produce NPY, but also sensitised other parts of the brain to produce additional receptors or ‘docking stations’ for the molecule — supercharging appetite even further.

“What we have uncovered is a vicious cycle that disrupts the body’s ability to balance its energy input with energy storage and enhances obesity development.”

Researchers have pinpointed a subset of neurons in the brain (green) that drive appetite under obesity. Image credit: Dr Yue Qi.

Herzog explained that the brain is wired to resist energy deficiency or weight loss, as it sees this as a threat to its survival. It thus kickstarts the mechanisms that increase appetite so that we seek out food — even when we have excess energy (fat) stored in the body. The researchers’ discovery opens the possibility of blocking the additional, more sensitised receptors for NPY as a new approach to developing anti-obesity medication.

“Our study addresses a longstanding question about how appetite is controlled in obesity and has the potential to take the development of therapy into a new direction,” Herzog said.

Top image credit: iStock.com/towfiqu ahamed