Stressing the link between Ghrelin and obesity

By Ievy Stamatov

Imagine for an instant that you are a zebra in the savannah, and all of a sudden you’re being chased by a lion. In order to escape the predator you have to generate a sufficient energetic output; you need your heart to beat faster, your lungs to let in more air. This response would require instant energy, and to acquire this energy, the body would need to feed off of simple fuel like sugars. In opting for these quick fuel sources, difficult-to-reach energy, like fat, is put on hold in the body.

As Alfonso Abizaid, assistant professor in Carleton’s Department of Neuroscience, explained in his laboratory located in the Life Sciences Research Building, this scenario is a rough illustration of the human body’s stress response.

“All of these biological reactions are useful in the short term because they help you escape the lion. But if you were being chased by lions 24 hours a day, this would be unsustainable. Today, this is what happens a lot of the time with stress especially if this stress is continuous.”

Dr. Abizaid is fascinated by how the brain works to regulate what we do with the nutrients consumed through food.

“Why is it that some people take more food than others, and why is that some people need to take more food than others?” he asks. This question almost floats in the air, inviting reflection. It’s this curiosity inherent in him that seems to drive Abizaid’s passion for research.

The human body’s capacity to store fat has been essential to our survival for thousands of generations; we naturally seek out foods that are high in fat and carbohydrates. But the problem is that the modern human now lives a relatively sedentary lifestyle, and yet life still brings challenges that require our primal energy instincts to kick in — challenges like stress. Abizaid’s work, funded by a generous operating grant from the Canadian Institutes of Health Research (CIHR) and executed with assistance from a team of graduate students including award-winning Carleton PhD candidate Zack Patterson, particularly looks into the connection between stress, obesity, and Ghrelin — a hormone secreted by the stomach. Ghrelin is the only peripheral hormone that stimulates hunger, and acts directly on a number of tissues including the brain to promote hunger and increases in body fat content. Thus, if someone has chronically elevated levels of Ghrelin in their system, even if they don’t overeat, they may put on fat.

Since being funded by CIHR, one of the notable findings from Dr. Abizaid’s research has been that Ghrelin is released not just when you’re hungry, but also when you’re stressed — especially if that stress is caused by social factors. Chronic social stressors such as harassment cause a spike in Ghrelin levels which, when observed in mice, increases food intake by about 20 percent. A subsequent experiment conducted by Abizaid’s team demonstrated that genetically engineered mice that lack the receptors that sense Ghrelin did not consume more food when put under the same stressful conditions as normal mice. Dr. Abizaid hopes these findings will contribute to the development of pharmacological agents that will help treat those vulnerable to stress by blocking Ghrelin receptors in the human brain, helping regulate metabolism and avoid metabolic disorders like Type-2 Diabetes.

Moving forward, Dr. Abizaid is setting his sights on pinpointing what areas of the brain are important for Ghrelin’s action in guiding metabolism, and looking deeper into if and how Ghrelin plays a role in maintaining mental health in situations of stress.

“Understanding the basic mechanisms by which Ghrelin and other hormones act in the brain during stress is critical for understanding not just body weight regulation, but also the overall maintenance of mental health. We want to understand if this hormone is also important as a neuro-protective mechanism in the face of stress.”

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