A hormone found to reverse obesity in mice has revealed important insights into how the brain regulates body weight. Researchers at the University of Oklahoma studied fibroblast growth factor 21 (FGF21) and discovered that it affects a crucial brain area involved in appetite and metabolism. This area is also influenced by popular weight-loss medications known as GLP-1 drugs. Their research was published in the journal Cell Reports.
Unlike other metabolic signals that target organs like the liver, FGF21 primarily operates through the brain. There is increasing interest in FGF21, particularly as drugs that target its pathway are being developed for treating metabolic dysfunction-associated steatohepatitis (MASH), a severe liver condition linked to obesity and insulin resistance.
The study, led by Dr. Matthew Potthoff, identified the hindbrain as the main site where FGF21 acts. This region is vital for managing essential functions such as hunger, energy balance, and nausea. Potthoff noted that previous research showed FGF21 signals the brain instead of the liver, but the specific brain area was unknown until now. Surprisingly, it appears that the hormone communicates with the hindbrain rather than the hypothalamus, where other body weight regulators are thought to act.
FGF21 specifically targets areas in the hindbrain called the nucleus of the solitary tract and the area postrema. This pathway is essential for FGF21 to exert its effects on metabolism and weight loss.
Potthoff hopes this research will lead to targeted therapies for obesity and MASH that minimise side effects commonly associated with FGF21 analogs, such as gastrointestinal issues. He emphasised the need for further studies to confirm if this brain circuit can help reverse MASH as well.
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