FGF21 hormone drives protein-specific appetite and reward in the brain

When faced with multiple food options and ultimately choosing one, the factors of that decision-making process may be more physiological than previously assumed. A group of scientists led by Pennington Biomedical Research Center's Dr. Christopher Morrison recently discovered that the hormone fibroblast growth factor 21, or FGF21, plays an influential role in brain reward mechanisms like those involved in dietary choices. 

The discovery was announced in the research team's recent paper titled "FGF21 acts in the brain to drive macronutrient-specific changes in behavioral motivation and brain reward signaling," which was published in the January 2025 issue of the journal Molecular Metabolism. The study data indicate that the FGF21 hormone acts on the brain to induce a protein-specific appetite by enhancing the reward value of foods that contain protein. 

What's fascinating is that this isn't just general hunger – it's a very specific appetite for protein. When protein is restricted, FGF21 acts in the brain to flip a molecular switch that makes protein-rich foods more rewarding and motivates animals to seek them out. Many people struggle to maintain a balanced diet. Understanding how the body naturally regulates protein appetite could lead to better strategies for promoting healthy eating." 

Dr. Christopher Morrison, Associate Executive Director of Basic Science at Pennington Biomedical

In the study, animals on a low-protein diet worked especially hard for liquid protein rewards, but not carbohydrate, fatty, or sweet rewards, compared to those on a normal diet. However, if FGF21's ability to act in the brain was disrupted, this protein-specific motivation was lost. 

The researchers then used a sophisticated neuroscience technique called fiber photometry to assess how nutrients activate dopamine neurons within the ventral tegmental area, or VTA, a brain region associated with reward. They discovered that protein restriction shifts the dopamine response, with carbohydrate more strongly activating dopamine neurons in control animals and protein more strongly activating dopamine neurons in protein-restricted animals. Importantly, this shift in reward signaling was lost in animals lacking FGF21. 

"It's a remarkable example of how hormone signals can tune the brain's reward system to drive specific nutritional appetites," explains Dr. Morrison. 

"This recent discovery demonstrates the continual journey to uncover the functions of certain genes, proteins and nutrients in our bodies while also highlighting the principal value that Pennington Biomedical delivers to the broader scientific community," said Dr. John Kirwan, Executive Director of Pennington Biomedical. "Understanding how the brain drives specific nutritional preferences has been a long-standing challenge in metabolism research. This work exemplifies how Pennington Biomedical's integrative approach - combining molecular biology, neuroscience, and behavioral studies - can unlock complex biological mysteries. I commend Dr. Morrison and his team for this extensive study, and I look forward to the additional discoveries that will emerge because of this one." 

The FGF21 hormone is produced in the liver and has been previously recognized as a regulator of energy balance and for its role in glucose metabolism. This newly published research emphasizes its significant impact on the central nervous system. 

This study was supported by grants from the National Institutes of Health and reflects Pennington Biomedical's commitment to advancing understanding of the biological mechanisms underlying nutrition and metabolism.