Calorie Restriction, Tirzepatide, and Hormone Signaling
When Dr. Wendy McKimpson arrived at Emory University in January, she brought not only a deep expertise in cell biology but also a personal passion for improving diabetes care. As an assistant professor in the Division of Digestive Diseases, Department of Medicine, McKimpson has spent the last nine months establishing her lab and building collaborations that blend basic science, clinical research, and translational work.
“It’s been a really exciting time for me,” McKimpson said. “One thing that I’ve been really excited about at Emory, something I haven’t necessarily seen at other places is the connection between all the different centers. As a basic scientist, it’s inspiring to be in an environment that mixes basic science, clinical work, and translational research. I want my research to eventually lead to treatments, and Emory has the pipeline to make that happen.”
McKimpson’s research focuses on hormone-producing endocrine cells in the pancreas and gut, cells that play central roles in the development of both diabetes and obesity. These cells are rare, making up just 1% of the pancreas, yet their dysfunction can trigger serious disease. “A constant challenge is making sure our models are relevant to human disease,” she noted. “How do these cells behave in culture, in mice, and in humans? That’s always on my mind.”
Her most recent study explores how calorie restriction affects hormone-producing cells in the stomach. Previous research linked calorie restriction to longer lifespan and increased levels of the hormone ghrelin, which signals to the brain. But the mechanisms behind this were unclear.
“What we found was not only more ghrelin-producing cells with calorie restriction but a whole program activated that increased multiple hormone-producing cells in the stomach,” McKimpson said. “Interestingly, when we treated mice with tirzepatide, a drug in the GLP-1 and GIP mimetic class used for obesity and diabetes, we saw a similar response, even in healthy mice.”
Fluorescence imaging of stomach tissue isolated from wild type mice treated with the incretin mimetic tirzepatide. This shows there is an increase in gastric endocrine cells (green, labeled with chromograninA) as well as those cells that produce the hormone ghrelin (red) after tirzepatide treatment. Cell nuclei are counterstained with DAPI (blue).
While ghrelin stimulates appetite, its increase in this context appeared linked to metabolic benefits. “Even without measuring hunger directly, we saw protective effects on glucose levels,” she explained. “We think these drugs are having beneficial effects in ways we don’t yet fully understand.”
The findings could help scientists design targeted therapies that capture the benefits of calorie restriction without triggering weight loss in patients who don’t need it. “If we understand how these drugs signal to other tissues—like how they alter cell abundance in the GI tract—we could develop new therapies that mimic these effects more precisely,” she said.
Beyond the lab, McKimpson is intentional about her role as a mentor. “I love working with students, from high school to postdocs,” she said. “It’s important to create an environment where everyone feels their ideas matter. I encourage all my trainees to have an independent project, no matter their level. Sometimes the most creative thinking comes from people who haven’t learned the ‘rules’ yet.”
Looking ahead, her team is investigating how these stomach cell changes differ in obesity and diabetes. Early results suggest the process may become dysregulated, raising questions about whether the body is attempting to compensate or if the cells are failing.
“We’re also seeing that calorie restriction affects progenitor cells—the ones that give rise to hormone-producing cells,” McKimpson added. “That’s important for thinking about future cellular therapies. Sometimes we need to target earlier in the cell’s life cycle, not just the finished product.”
For McKimpson, the work is both personal and scientific. “At the end of the day, my goal is to uncover new ways to protect and restore these critical cells,” she said. "If we can do that, we can move one step closer to better therapies for people living with diabetes and obesity."