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, eating patterns and physical activity levels are key contributors.
A team at the Garvan Institute of Medical Research has discovered a group of brain cells that boosts appetite when there is a prolonged surplus of energy in the body, such as excess fat accumulation in obesity.
The researchers discovered that these cells not only produced the appetite-stimulating molecule NPY, but they in fact made the brain more sensitive to the molecule, boosting appetite even more.
“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,” explains Professor Herbert Herzog, senior author of the study.
“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. 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,” says Professor Herzog.
“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 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.”
Yue Qi, Nicola J. Lee, Chi Kin Ip, Ronaldo Enriquez, Ramon Tasan, Lei Zhang, Herbert Herzog. Agrp-negative arcuate NPY neurons drive feeding under positive energy balance via altering leptin responsiveness in POMC neurons. Cell Metabolism, 2023; DOI: 10.1016/j.cmet.2023.04.020
Garvan Institute of Medical Research. “Researchers pinpoint brain cells that drive appetite in obesity.” ScienceDaily. ScienceDaily, 17 May 2023. <www.sciencedaily.com/releases/2023/05/230517121529.htm>.
Photo by Anastassia Chepinska