Scientists at the University of Oklahoma have identified how a naturally occurring hormone, FGF21, can reverse obesity in mice by acting on a specific brain circuit. The findings, published in Cell Reports, shed new light on how metabolism and body weight are regulated.
The study shows that FGF21 signals to the hindbrain—rather than the hypothalamus, as previously assumed—targeting regions known as the nucleus of the solitary tract and area postrema. These areas communicate with the parabrachial nucleus, forming a circuit that drives metabolic changes and fat burning.
This pathway overlaps with brain regions affected by GLP-1 drugs, though the mechanisms differ. While GLP-1 treatments primarily suppress appetite, FGF21 increases energy expenditure, enabling the body to burn more calories.
The discovery could guide the development of more targeted therapies for obesity and metabolic diseases. FGF21-based drugs are already under investigation for MASH, and understanding its brain-based mechanism may help reduce side effects and improve treatment precision.
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