What is ghrelin? Rethinking the body’s ‘hunger hormone’

Hormones influence how we feel — happy, sad or hungry — and profoundly shape how our bodies function and respond to disease.

For years, ghrelin has been widely known as the body’s “hunger hormone,” the signal that tells us when it is time to eat. But research from Texas A&M AgriLife Research suggests ghrelin’s role in the body is far more complex.

For more than two decades, Yuxiang Sun, M.D., Ph.D., has reshaped scientific understanding of ghrelin, uncovering its effects on multiple systems in the body, from metabolism and inflammation to aging and brain health.

Sun is a professor in the Texas A&M College of Agriculture and Life SciencesDepartment of Nutrition and the interim associate director for precision nutrition with the Institute for Advancing Health through Agriculture. Her research has delved into all sorts of biological spaces, including metabolism, inflammation, aging and neurodegenerative disease – but what she is best known for is her work on ghrelin signaling.

Ghrelin does a lot more than its nickname suggests – in fact, ghrelin plays a much broader biological role than scientists once believed.

“My passion is to explain things,” Sun said. “Trained as an M.D., my work always starts with a medically relevant question, then hopefully our work contributes to greater scientific understanding.”

Changing the game for ghrelin research

Ghrelin was discovered in 1999. Early work in the field was focused on what ghrelin does when administered pharmacologically – that is, in drug form. However, there was no work on what ghrelin did physiologically. To address this gap, Sun led foundational research on ghrelin and ghrelin-receptor knockouts.

“I feel very lucky to have generated those key models for the field. “When you administer something pharmacologically, that’s one thing – but knocking out a gene globally in an organism is totally different.”

Previous work on ghrelin in drug-form had proved that it increased appetite, food intake and growth hormone levels.

Sun was expecting that a lack of ghrelin signaling would lead to the opposite result: reduced appetite, less food intake and attenuated growth. To her surprise, there was no effect on any of these when the ghrelin gene was absent. The discrepancy between pharmacological and physiological gene-deletion effects has raised considerably opposing opinions in the field.

“My career has been a lot of making lemonade out of lemons,” Sun said. “The ghrelin knockouts went totally against what people expected and believed. As a post-doc, I struggled with this a lot.”

To overcome the doubt of the field, she decided to further study ghrelin under genetic obesity condition. Again, surprisingly a lack of ghrelin didn’t reduce obesity as expected. What was most exciting to her, though, was the discovery that blood glucose levels stabilized when ghrelin was absent.

“This was the first time ghrelin was linked to diabetes,” Sun said.

Her follow up work showed that in addition to being the “hunger hormone,” ghrelin acted as a diabetic regulator. This was the beginning of Sun’s career of uncovering all the different biological functions of ghrelin.

Ghrelin in aging and inflammation

Sun found that ghrelin is a very dynamic hormone, playing roles in hunger and appetite, mood, body temperature, immune system function, aging and much more.

Ghrelin’s “hunger hormone” title kept a lot of scientists from endeavoring to learn more about it’s broader capabilities. Ghrelin was extensively studied in the brain, since that was where its receptor was known to be located.

Sun had already started to understand that there was more to ghrelin’s biological function, such as uncovering its role in diabetes. She then made the connection between ghrelin and inflammation when she attended a neuroscience talk, by chance. She noticed a figure in the speakers slides looked familiar.

“The speaker showed this image of macrophages distributed throughout the human body, and it looked just like the distribution of the ghrelin figure we had made for a review paper we were writing,” she said. “I thought – what are the chances that the ghrelin receptor is expressed in macrophages, and that they act as carriers of this receptor to different organs of the body?”

Once again, her hypothesis proved to be correct. Her lab published the initial finding that the ghrelin receptor was expressed in macrophages in 2016 in the journal Aging, where they also explored the links between ghrelin and thermogenesis.

Since then, Sun has been intrigued by the interaction of different fields: metabolism, immunity, cancer, aging and neurodegenerative disease.

Looking forward: Sun’s ongoing work

Of her interdisciplinary interests, what most excites Sun now is inflammation and aging, or “inflammaging”, as she likes to say.

Her next series of questions will focus on ghrelin’s role in neuroinflammation and Alzheimer’s disease. Her lab’s proposal for this work was one of 10 selected for funding, out of over 100 submissions, by Texas A&M Health’s Dementia and Alzheimer’s Research Initiative.

“I care about quality of life for our aging population, and I feel a lot of medical intervention is too late,” Sun said. “Early disease prevention to decrease risk factors ultimately is what will make a difference for this population.”

Building on a two-decade scholarly journey, Sun’s work will continue to advance the understanding of ghrelin in health and disease, contributing to the prevention and treatment of chronic diseases with the ultimate goal of improving quality of life.

This article was originally published on Newswise: Nutrition.