The brain cells that drive appetite in obesity have been pinpointed, offering hope for new treatments.
Australian scientists found a “vicious cycle” that disrupts the body’s ability to balance its energy input with energy storage – leading to people piling on the pounds.
The research team says their discovery opens the possibility of a “new approach” to developing anti-obesity medications.
They found that a group of brain cells boost appetite when there is a prolonged surplus of energy in the body, such as excess fat accumulation in obesity.
The researchers discovered that those cells not only produced the appetite-stimulating molecule NPY, but they in fact made the brain more sensitive to the molecule, boosting appetite even further.
Study senior author Professor Herbert Herzog said: “These cells kickstart changes in the brain that make it more sensitive to even low levels of NPY when there is a surplus of energy in the body in the form of excess fat – driving appetite during obesity.
“Our study addresses a long-standing question about how appetite is controlled in obesity and has the potential to take the development of therapy into a new direction.”
Obesity affects more than one in 10 adults, and increases a person’s risk of developing other chronic conditions, including diabetes and heart disease.
Eating patterns and physical activity levels are key contributors to obesity.
Prof. Herzog, a visiting scientist at Garvan Institute of Medical Research in New South Wales, said: “Our brain has intricate mechanisms that sense how much energy is stored in our body and adjust our appetite accordingly.
“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 Garvan researchers investigated cells in the brain called neurons that produced NPY and discovered that, surprisingly, 15 percent of them were different – they did not shut down NPY production during obesity.
Prof. Herzog said: “We found that under obese conditions, appetite was mostly driven by NPY produced by this subset of neurons.
“These cells did not only produce NPY, but also sensitized 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.
“Our brain is wired to resist energy deficiency or weight loss, as it sees this as a threat to our survival and kickstarts mechanisms that increase our appetite so that we seek out food.
“As we found now, this even occurs when we have excess energy stored in the body.”
The researchers say their discovery, published in the journal Cell Metabolism, opens the possibility of blocking the additional, more sensitized receptors for NPY as a new approach to developing anti-obesity medication.
Prof. Herzog added: “Our discovery helps us better understand the mechanisms in the brain that interfere with a balanced energy metabolism and how they may be targeted to improve health.”