Researchers at Pennington Biomedical Research Center provide critical insight into how the brain and body work together to regulate food intake, energy use and metabolism – offering important new analysis into the biology of obesity and metabolic health.
The study, “ FGF21 signals through hindbrain neurons to alter food intake and energy expenditure during dietary protein restriction ,” published in the journal Cell Reports and led by Pennington Biomedical Associate Executive Director for Basic Science Dr. Christopher Morrison and colleagues, focuses on Fibroblast Growth Factor 21 (FGF21), a hormone produced by the liver that helps the body adapt to changes in diet and nutritional status.
Researchers identified a specific group of neurons in the hindbrain that respond directly to FGF21, acting as a key pathway through which the hormone influences eating behavior and energy balance. These neurons play a central role in adapting to dietary protein restriction by altering both food intake and energy expenditure.
The findings demonstrate that signaling through these hindbrain neurons is required to drive metabolic adaptations, including changes in appetite and calorie burning. This challenges long-standing assumptions that these processes are primarily controlled by other regions of the brain and points to a more complex, integrated system.
Research also shows that these neurons are both necessary and sufficient to drive changes in food intake, food choice and energy expenditure during protein restriction – underscoring their central role in maintaining energy balance.
“This work highlights how strongly nutrition is linked to brain function. The body is constantly monitoring what we eat and making ongoing adjustments, so understanding those signals is key to improving metabolic health,” said Dr. Morrison, who is co-director of the Neurosignaling Laboratory at Pennington Biomedical . “These findings suggest that FGF21-based therapies could potentially be optimized to target specific brain circuits, and that clinical end points beyond liver fat, such as dietary behavior and metabolic rate, may be worth evaluating.”
Obesity, diabetes and related metabolic conditions continue to pose significant health challenges worldwide. Obesity and metabolic diseases are driven in part by disruptions in how the body regulates energy balance. By identifying the pathways that connect diet to brain function, researchers are gaining critical insight into how to better treat these conditions.
FGF21-based therapies are already being explored in clinical settings, and understanding how these therapies work at the neural level is essential for improving their effectiveness and minimizing side effects.
“This study is an excellent example of why basic science research is so important to improving human health,” said Dr. Jennifer Rood, Interim Senior Vice Chancellor and Executive Director of Pennington Biomedical. “By uncovering how the brain and body communicate, our scientists are helping to build the foundation for new treatments for obesity and metabolic disease.”
This study was supported by funding through the National Institutes of Health, and the authors would also like to thank the leadership and staff of the Pennington Biomedical Comparative Biology Core and Animal Metabolism and Behavior Core for their skillful assistance and excellent technical support.
In addition to Dr. Morrison, other researchers from Pennington Biomedical included Drs. Redin Spann, Sora Kim, Shahjalal Khan, Diana Albarado, Sun Fernandez-Kim, Hans-Rudolf Berthoud, David McDougal, Heike Münzberg-Gruening, Yanlin He and Sangho Yu.
Media Note:
Dr. Christopher Morrison, along with Dr. Matthew Potthoff from University of Oklahoma College of Medicine, conducted a Q&A with Cell Reports about their research into FGF21.
About the Pennington Biomedical Research Center
The Pennington Biomedical Research Center is at the forefront of medical discovery as it relates to understanding the triggers of obesity, diabetes, cardiovascular disease, cancer and dementia. Pennington Biomedical has the vision to lead the world in promoting nutrition and metabolic health and eliminating metabolic disease through scientific discoveries that create solutions from cells to society. The Center conducts basic, clinical and population research, and is a campus in the LSU System.
The research enterprise at Pennington Biomedical includes over 600 employees within a network of 44 clinics and research laboratories, and 16 highly specialized core service facilities. Its scientists and physician/scientists are supported by research trainees, lab technicians, nurses, dietitians and other support personnel. Pennington Biomedical is a globally recognized state-of-the-art research institution in Baton Rouge, Louisiana. For more information, see www.pbrc.edu .
Cell Reports
Animals
FGF21 signals through hindbrain neurons to alter food intake and energy expenditure during dietary protein restriction
28-Apr-2026
The authors declare no competing interests.