Scientists Uncover Neurons Driving Increased Appetite in Obesity

Obesity
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Researchers at the Garvan Institute of Medical Research in Australia, have discovered a subset of neurons that lead to an increased appetite in patients with obesity upon prolonged exposure to an excess of fat in the body.

According to data from the National Health and Nutrition Examination Survey, nearly one in every three adults in the U.S. are considered overweight—and that number is on the rise. Serious consequences of the condition, such as cardiovascular disease, type two diabetes and musculoskeletal disorders, reveal the urgent need for a better understanding of the underlying mechanisms of the disease.

Reporting in Cell Metabolism, scientists have discovered that neurons located in the hypothalamus—a region of the brain that regulates feeding, express an appetite stimulating peptide called neuropeptide Y (NPY) in response to a prolonged surplus of energy in the body. In addition to releasing NPY, the cells also increase the brains sensitivity to the molecule, leading to a viscous cycle of feeling hungry.

“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,” explained Herbert Herzog, Visiting Scientist at Garvan and senior author of the study in a press statement.

“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.”

For their research, the scientists used mouse models of obesity and investigated the function of the NPY-producing neurons specifically. The researchers discovered that opto-genetic silencing of the neurons in mice, led to a decrease in food intake, revealing the proteins’ important role in obesity pathology.

The scientists believe that the results of their study could be used in the future to potentially target and inhibit the additional sensitized NPY receptors in the body as a possible new approach in obesity therapies.

“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 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,” Herzog concluded in a press statement.

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