Central FGF21 production regulates memory but not peripheral metabolism

Area of Science:

• Neuroendocrinology
• Metabolic regulation
• Cognitive neuroscience

Background:

• Fibroblast growth factor 21 (FGF21) is a liver-derived hormone regulating energy and nutrient intake.
• Previous studies suggested FGF21 originates in the hypothalamus, impacting lipid metabolism.

Purpose of the Study:

• To rigorously investigate the expression and function of FGF21 within the brain.
• To clarify the source and central effects of FGF21 on cognition and metabolism.

Main Methods:

• Utilized a mouse model with CRE recombinase targeting FGF21-expressing cells.
• Investigated FGF21 expression localization using genetic tools.
• Assessed the impact of central FGF21 on spatial memory, energy homeostasis, and sugar intake.
• Examined FGF21 effects on hippocampal long-term potentiation and neuronal activation.

Main Results:

• Demonstrated that FGF21 is primarily expressed in the retrosplenial cortex (RSC), not the hypothalamus.
• Showed that central FGF21 from the RSC enhances spatial memory.
• Found no significant regulation of energy homeostasis or sugar intake by central FGF21.
• Observed that FGF21 administration prolongs hippocampal long-term potentiation and enhances neuronal activation.

Conclusions:

• Endogenous FGF21 in the brain originates from the RSC and plays a role in spatial memory.
• FGF21 influences hippocampal function, enhancing long-term potentiation and neuronal activity.
• Central FGF21's primary role appears to be in cognitive functions, specifically spatial memory, rather than metabolic regulation.